Determination of the enrichment of the hydrogen bound to carbon 5 of glucose on 2H2O administration.
Explore the source record for details and available documents.
Carbon↗
Biomedical subjects
V Chandramouli
Publications and source records attributed to V Chandramouli.
Quantitative contributions of gluconeogenesis to glucose production during fasting in type 2 diabetes mellitus.
Contributions of gluconeogenesis to glucose production were determined between 14 to 22 hours into a fast in type 2 diabetics (n = 9) and age-weight-matched controls (n = 7); ages, 60.4 +/- 2.3 versus 55.6 +/- 1.2 years and body mass indices (BMI) 28.6 +/- 2.3 versus 26.6 +/- 0.8 kg/m2. Production was measured using a primed-continuous [6,6-2H2]glucose infusion and gluconeogenesis from 2H enrichment at carbons 2 and 5 of blood glucose on 2H2O ingestion. Plasma glucose concentration declined from 9.6 +/- 0.6 at 14 hours to 7.3 +/- 0.6 at 22 hours in the diabetics (P = .001) and from 5.4 +/- 0.1 to 5.0 +/- 0.1 in the controls (P < .05). Production from the 17th to 22nd hour declined 27.1% +/- 0.6% in the diabetics versus 18.5% +/- 0.8% in the controls (P = .001); from 10.4 +/- 0.3 to 7.6 +/- 0.2 versus 10.0 +/- 0.4 to 8.2 +/- 0.4 micromol/kg/min. Percent contributions of gluconeogenesis to production measured at 1 1/2 to 2-hour intervals beginning the 15th hour were 6.8% +/- 1.0% more in the diabetics than controls. The quantity of glucose contributed by gluconeogenesis declined 19.8% +/- 3.8% (P < .001) in the diabetics and 6.9% +/- 2.3% in the controls (P = .05); 7.21 +/- 0.32 to 5.74 +/- 0.26 versus 6.20 +/- 0.28 to 5.75 +/- 0.24 micromol/kg/min. The contribution of glycogenolysis to production, estimated from the difference between production and gluconeogenesis, declined to the same extent in diabetic and control subjects, 40.7% +/- 6.6% and 37.7% +/- 4.1%; from 3.23 +/- 0.35 to 1.86 +/- 0.26 versus 3.81 +/- 0.22 to 2.42 +/- 0.28 micromol/kg/min. Thus, gluconeogenesis contributed more to glucose production in the diabetic than control subjects. Production and the contribution of gluconeogenesis declined more in the diabetic subjects during the fast. The factors regulating these changes remain uncertain.
Deuterium↗
The impact of immunization record aggregation on up-to-date rates--implications for immunization registries in rural areas.
Problems with poorly documented immunization records may be especially important in rural areas. To evaluate the potential impact of a regional registry in a rural region, this study quantified the change in documented immunization rates for nine primary care sites in rural Colorado resulting from the addition of public health department immunization clinic records. Manual chart reviews of immunization data were conducted at both private primary care and public health department sites in two geographic areas in rural Colorado. Data from private primary care sites were matched to data from the public health department sites. Immunization up-to-date (UTD) rates at each primary care site were then recalculated for 12- and 24-month-olds after including data from public health department sites. Of 1,533 children, 469 (31 percent) were given immunizations at both a private primary care and a public health department site. The UTD rate (3:2:3:2) of 12-month-olds using only data from primary care sites ranged from 32 to 79 percent. Including the public health department data increased the rates by 0 to 26 percent (mean = 11 percent) for 12-month-old children. The UTD rate of 24-month-olds (4:3:1:3 and any Hib on/after 12 months) ranged from 6 to 54 percent at the primary care sites. These rates increased by 6 to 21 percent (mean = 12 percent) when public health department data were added. This "virtual" registry combining primary care and public health department data increased calculated immunization rates at primary care sites substantially, with a range of 0 to 26 percent.
Colorado↗
Sources of blood glycerol during fasting.
To determine the source(s) of blood and very low density lipoprotein (VLDL)-triglyceride glycerol during fasting, four men ingested (2)H(2)O from 14 to 20 h into a 60-h fast to achieve ~0.5% body water enrichment. At 60 h of fasting, glycerol flux was measured using [2-(14)C]glycerol. Blood was taken for measurement of (2)H enrichment at carbon 6 of glucose and at carbon 3 of free glycerol and VLDL-triglyceride glycerol. (2)H enrichment of the 2 hydrogens bound to carbon 3 of VLDL-triglyceride glycerol was 105 +/- 2% of the (2)H enrichment of the 2 hydrogens bound to carbon 6 of glucose, indicating isotopic equilibrium between hepatic glyceraldehyde 3-P and glycerol 3-P. The (2)H enrichment of the 2 hydrogens bound to carbon 3 of free glycerol was 17 +/- 3% of VLDL-triglyceride glycerol, indicating that a significant percentage of free glycerol in blood originated from the hydrolysis of circulating VLDL-triglyceride or a pool of glycerol with similar (2)H enrichment. Glycerol flux was 6.3 +/- 1.1 micromol. kg(-1). min(-1). Glycerol appearing from nonadipose tissue sources was then approximately 1.1 micromol. kg(-1). min(-1). Seven other subjects were fasted for 12, 42, and 60 h. A small percentage of glycerol in the circulation after 12 h of fasting was enriched with (2)H. The enrichment of the 2 hydrogens bound to carbon 3 of free glycerol in the longer periods of fasting was approximately 16% of the enrichment of the 2 hydrogens bound to carbon 6 of glucose. Therefore, as much as 15-20% of systemic glycerol turnover during fasting is not from lipolysis of adipose tissue triglyceride.
Adult↗
Delivery of pediatric after-hours care by call centers: a multicenter study of parental perceptions and compliance.
BACKGROUND: Despite the rapid growth of centralized call centers to provide after-hours triage to patients of multiple providers, little is known about the perceptions of parents regarding this type of care and their compliance with triage disposition recommendations. DESIGN/METHODS: From August through September 1999, randomized samples of after-hours calls were selected each day from computerized records at 4 pediatric call centers at 1) Children's Hospital, Denver, Colorado; 2) Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; 3) Rainbow Babies and Children's Hospital, Cleveland, Ohio; and 4) All Children's Hospital, St Petersburg, Florida. All participating call centers use the same triage software. Calls were randomly selected to yield at least 250 callers with nonurgent dispositions and 100 with urgent dispositions from each site. Telephone surveys to callers were conducted by an external survey unit 3 to 7 days after the call to the call center. RESULTS: Surveys were completed for 70.5% of those sampled (N = 1561). Parents indicated they were very satisfied or satisfied with aspects of care received from 92.6% (waiting time) to 99.4% (nurse courteousness) of the time. Satisfaction did not differ by site or by recommended disposition of the index call. Most parents (65.2%) reported no preference about speaking with a physician or nonphysician for after-hours care, whereas 27.7% preferred to speak with a physician. Usually speaking with a physician during office hours (odds ratio [OR]: 1.48), feeling it was important that provider knows child's medical history (OR: 3.47), and respondent having an educational level of college graduate or higher (OR: 1.30) were significant predictors of preferring to speak with a physician. Of the 37.0% (N = 723) of parents who reported any change in their relationship with their primary provider as a result of the after-hours call center, 95.7% (N = 691) assessed the change to be positive. Reported compliance with the call center disposition recommendation was 83.3% for urgent referral, 41.0% for next day, 4.5% for visit at a later time, and 78.2% for home care. The major reason given by parents for noncompliance was reporting that they heard a different disposition (76.9% for urgent to 100% for visit at a later time). CONCLUSIONS: Parental satisfaction with pediatric call centers was uniformly high in 4 different geographic locations, and almost all parents who reported any effect on their relationship with their primary provider assessed it as positive. Compliance with recommendations for urgent evaluation or home care was relatively high but for intermediary dispositions was low. In most cases in which noncompliance occurred, parents reported hearing a different disposition. Additional study is needed to clarify whether noncompliance, especially in cases in which an urgent recommendations was made, is attributable to poor nurse communication of the recommended disposition, parental misinterpretation, or parental difference of opinion.
Community Health Services↗
Small increases in insulin inhibit hepatic glucose production solely caused by an effect on glycogen metabolism.
Based on our earlier work, a 2.5-fold increase in insulin secretion should completely inhibit hepatic glucose production through the hormone's direct effect on hepatic glycogen metabolism. The aim of the present study was to test the accuracy of this prediction and to confirm that gluconeogenic flux, as measured by three independent techniques, was unaffected by the increase in insulin. A 40-min basal period was followed by a 180-min experimental period in which an increase in insulin was induced, with euglycemia maintained by peripheral glucose infusion. Arterial and hepatic sinusoidal insulin levels increased from 10 +/- 2 to 19 +/- 3 and 20 +/- 4 to 45 +/- 5 microU/ml, respectively. Net hepatic glucose output decreased rapidly from 1.90 +/- 0.13 to 0.23 +/- 0.16 mg. kg(-1). min(-1). Three methods of measuring gluconeogenesis and glycogenolysis were used: 1) the hepatic arteriovenous difference technique (n = 8), 2) the [(14)C]phosphoenolpyruvate technique (n = 4), and 3) the (2)H(2)O technique (n = 4). The net hepatic glycogenolytic rate decreased from 1.72 +/- 0.20 to -0.28 +/- 0.15 mg. kg(-1). min(-1) (P < 0.05), whereas none of the above methods showed a significant change in hepatic gluconeogenic flux (rate of conversion of phosphoenolpyruvate to glucose-6-phosphate). These results indicate that liver glycogenolysis is acutely sensitive to small changes in plasma insulin, whereas gluconeogenic flux is not.
Animals↗
A probing dose of phenylacetate does not affect glucose production and gluconeogenesis in humans.
Phenylacetate ingestion has been used to probe Krebs cycle metabolism and to augment waste nitrogen excretion in urea cycle disorders. Phenylalkanoic acids, including phenylacetate, have been proposed as potential therapeutic agents in the treatment of diabetes. They inhibit gluconeogenesis in the liver in vitro and reduce the blood glucose concentration in diabetic rats. The effect of sodium phenylacetate ingestion on blood glucose and the contribution of gluconeogenesis to glucose production have now been studied in 7 type 2 diabetic patients. The study was not designed to test whether the changes in glucose metabolism observed in the rat could be reproduced in humans. After an overnight fast, over a period of 1 hour, 4.8 g phenylacetate was ingested, which is the highest dose used to probe Krebs cycle metabolism. Glucose production was measured by tracer kinetics using [6,6-(2)H2]glucose and gluconeogenesis by the labeling of the hydrogens of blood glucose on (2)H20 ingestion. The concentration of phenylacetate in plasma peaked by 2 hours after its ingestion, and about 40% of the dose was excreted in 5 hours. The plasma glucose concentration and production, and the contribution of gluconeogenesis to glucose production, were unaffected by phenylacetate ingestion at the highest dose used to probe Krebs cycle metabolism.
Aged↗
Mechanism by which metformin reduces glucose production in type 2 diabetes.
To examine the mechanism by which metformin lowers endogenous glucose production in type 2 diabetic patients, we studied seven type 2 diabetic subjects, with fasting hyperglycemia (15.5 +/- 1.3 mmol/l), before and after 3 months of metformin treatment. Seven healthy subjects, matched for sex, age, and BMI, served as control subjects. Rates of net hepatic glycogenolysis, estimated by 13C nuclear magnetic resonance spectroscopy, were combined with estimates of contributions to glucose production of gluconeogenesis and glycogenolysis, measured by labeling of blood glucose by 2H from ingested 2H2O. Glucose production was measured using [6,6-2H2]glucose. The rate of glucose production was twice as high in the diabetic subjects as in control subjects (0.70 +/- 0.05 vs. 0.36 +/- 0.03 mmol x m(-2) min(-1), P < 0.0001). Metformin reduced that rate by 24% (to 0.53 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0009) and fasting plasma glucose concentration by 30% (to 10.8 +/- 0.9 mmol/l, P = 0.0002). The rate of gluconeogenesis was three times higher in the diabetic subjects than in the control subjects (0.59 +/- 0.03 vs. 0.18 +/- 0.03 mmol x m(-2) min(-1) and metformin reduced that rate by 36% (to 0.38 +/- 0.03 mmol x m(-2) x min(-1), P = 0.01). By the 2H2O method, there was a twofold increase in rates of gluconeogenesis in diabetic subjects (0.42 +/- 0.04 mmol m(-2) x min(-1), which decreased by 33% after metformin treatment (0.28 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0002). There was no glycogen cycling in the control subjects, but in the diabetic subjects, glycogen cycling contributed to 25% of glucose production and explains the differences between the two methods used. In conclusion, patients with poorly controlled type 2 diabetes have increased rates of endogenous glucose production, which can be attributed to increased rates of gluconeogenesis. Metformin lowered the rate of glucose production in these patients through a reduction in gluconeogenesis.
Calorimetry, Indirect↗
Prandial glucose effectiveness and fasting gluconeogenesis in insulin-resistant first-degree relatives of patients with type 2 diabetes.
Impaired glucose effectiveness (i.e., a diminished ability of glucose per se to facilitate its own metabolism), increased gluconeogenesis, and endogenous glucose release are, together with insulin resistance and beta-cell abnormalities, established features of type 2 diabetes. To explore aspects of the pathophysiology behind type 2 diabetes, we assessed in a group of healthy people prone to develop type 2 diabetes (n = 23), namely first-degree relatives of type 2 diabetic patients (FDR), 1) endogenous glucose release and fasting gluconeogenesis measured using the 2H2O technique and 2) glucose effectiveness. The FDR group was insulin resistant when compared with an age-, sex-, and BMI-matched control group without a family history of type 2 diabetes (n = 14) (M value, clamp: 6.07 +/- 0.48 vs. 8.06 +/- 0.69 mg x kg(-1) lean body weight (lbw) x min(-1); P = 0.02). Fasting rates of gluconeogenesis (1.28 +/- 0.06 vs. 1.41 +/- 0.07 mg x kg(-1) lbw x min(-1); FDR vs. control subjects, P = 0.18) did not differ in the two groups and accounted for 53 +/- 2 and 60 +/- 3% of total endogenous glucose release. Glucose effectiveness was examined using a combined somatostatin and insulin infusion (0.17 vs. 0.14 mU x kg(-1) x min(-1), FDR vs. control subjects), the latter replacing serum insulin at near baseline levels. In addition, a 360-min labeled glucose infusion was given to simulate a prandial glucose profile. After glucose infusion, the integrated plasma glucose response above baseline (1,817 +/- 94 vs. 1,789 +/- 141 mmol/l per 6 h), the ability of glucose to simulate its own uptake (1.50 +/- 0.13 vs. 1.32 +/- 0.16 ml x kg(-1) lbw x min(-1)), and the ability of glucose per se to suppress endogenous glucose release did not differ between the FDR and control group. In conclusion, in contrast to overt type 2 diabetic patients, healthy people at high risk of developing type 2 diabetes are characterized by normal glucose effectiveness at near-basal insulinemia and normal fasting rates of gluconeogenesis.
Adult↗
Effects of free fatty acid elevation on postabsorptive endogenous glucose production and gluconeogenesis in humans.
Effects of free fatty acids (FFAs) on endogenous glucose production (EGP) and gluconeogenesis (GNG) were examined in healthy subjects (n = 6) during stepwise increased Intralipid/heparin infusion (plasma FFAs 0.8+/-0.1, 1.8+/-0.2, and 2.8+/-0.3 mmol/l) and during glycerol infusion (plasma FFAs approximately 0.5 mmol/l). Rates of EGP were determined with D-[6,6-2H2]glucose and contributions of GNG from 2H enrichments in carbons 2 and 5 of blood glucose after 2H2O ingestion. Plasma glucose concentrations decreased by approximately 10% (P < 0.01), whereas plasma insulin increased by approximately 47% (P = 0.02) after 9 h of lipid infusion. EGP declined from 9.3+/-0.5 (lipid) and 9.0+/-0.8 pmol x kg(-1) x min(-1) (glycerol) to 8.4+/-0.5 and 8.2+/-0.7 micromol x kg(-1) x min(-1), respectively (P < 0.01). Contribution of GNG similarly rose (P < 0.01) from 46+/-4 and 52+/-3% to 65+/-8 and 78+/-7%. To exclude interaction of FFAs with insulin secretion, the study was repeated at fasting plasma insulin (approximately 35 pmol/l) and glucagon (approximately 90 ng/ml) concentrations using somatostatin-insulin-glucagon clamps. Plasma glucose increased by approximately 50% (P < 0.005) during lipid but decreased by approximately 12% during glycerol infusion (P < 0.005). EGP remained unchanged over the 9-h period (9.9+/-1.2 vs. 9.0+/-1.1 micromol x kg(-1) x min(-1)). GNG accounted for 62+/-5 (lipid) and 60+/-6% (glycerol) of EGP at time 0 and rose to 74+/-3% during lipid infusion only (P < 0.05 vs. glycerol: 64+/-4%). In conclusion, high plasma FFA concentrations increase the percent contribution of GNG to EGP and may contribute to increased rates of GNG in patients with type 2 diabetes.
Absorption↗
Reducing after-hours referrals by an after-hours call center with second-level physician triage.
OBJECTIVES: One-third of practices signing-out to The Children's Hospital Call Center in Denver, Colorado, choose to do second-level physician (SLP) triage for calls judged by the Center to require after-hours referral (AHR). We examined: 1) the effect of SLP triage on the rate of AHRs and 2) reasons for physicians' decisions. DESIGN: From January 1998 to August 1998 all calls from patients using a 5-member suburban pediatric practice judged by the Call Center to require AHR were referred to the practice's on-call physician who did SLP triage and completed a questionnaire. RESULTS: There were 955 eligible calls, 22% (N = 216) of which were initially given an urgent disposition by Call Center nurses. Physician questionnaires were completed for 97% (N = 209). Of patients initially triaged for AHR, 49% (N = 103) were subsequently given an AHR, 17% (N = 35) a next day office referral, and 34% (N = 71) home care and advice. Reasons for not urgently referring included the following: 1) medical problem didn't require urgent evaluation (95%, N = 99); 2) change in the patient's condition; (40% N = 43); 3) prior knowledge of family's ability to evaluate and care for the patient (40%, N = 43); and 4) knowledge of the patient's medical history (18%, N = 19). After SLP triage the overall urgent referral rate was 11%. CONCLUSIONS: Signing out to a Call Center decreased physicians' after-hours calls by 77% and SLP triage halved the number of urgent after-hours referrals.
Emergencies↗
Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis.
Net hepatic glycogenolysis and gluconeogenesis were examined in normal (n = 4) and cirrhotic (n = 8) subjects using two independent methods [13C nuclear magnetic resonance spectroscopy (NMR) and a 2H2O method]. Rates of net hepatic glycogenolysis were calculated by the change in hepatic glycogen content before ( approximately 11:00 PM) and after ( approximately 7:00 AM) an overnight fast using 13C NMR and magnetic resonance imaging. Gluconeogenesis was calculated as the difference between the rates of glucose production determined with an infusion of [6,6-2H2]glucose and net hepatic glycogenolysis. In addition, the contribution of gluconeogenesis to glucose production was determined by the 2H enrichment in C-5/C-2 of blood glucose after intake of 2H2O (5 ml/kg body water). Plasma levels of total and free insulin-like growth factor I (IGF-I) and IGF-I binding proteins-1 and -3 were significantly decreased in the cirrhotic subjects (P < 0.01 vs. controls). Postprandial hepatic glycogen concentrations were 34% lower in the cirrhotic subjects (P = 0.007). Rates of glucose production were similar between the cirrhotic and healthy subjects [9.0 +/- 0.9 and 10.0 +/- 0.8 micromol. kg body wt-1. min-1, respectively]. Net hepatic glycogenolysis was 3.5-fold lower in the cirrhotic subjects (P = 0.01) and accounted for only 13 +/- 6% of glucose production compared with 40 +/- 10% (P = 0.03) in the control subjects. Gluconeogenesis was markedly increased in the cirrhotic subjects and accounted for 87 +/- 6% of glucose production vs. controls: 60 +/- 10% (P = 0.03). Gluconeogenesis in the cirrhotic subjects, as determined from the 2H enrichment in glucose C-5/C-2, was also increased and accounted for 68 +/- 3% of glucose production compared with 54 +/- 2% (P = 0.02) in the control subjects. In conclusion, cirrhotic subjects have increased rates of gluconeogenesis and decreased rates of net hepatic glycogenolysis compared with control subjects. These alterations are likely important contributing factors to their altered carbohydrate metabolism.
Adult↗
Origins of the hydrogen bound to carbon 1 of glucose in fasting: significance in gluconeogenesis quantitation.
Healthy subjects ingested (2)H(2)O. (2)H enriched the hydrogen bound to carbon 1 of blood glucose 1.3 to 1.8 times more than the hydrogens bound to carbon 6. Enrichment at carbon 1 was more than at carbon 5 after 14 h, but not after 42 h, of fasting. After overnight fasting, when [2,3-(3)H]succinate was infused, 34 times as much (3)H was bound to carbon 6 as to carbon 1. On [1-(2)H,1-(3)H, 1-(14)C]galactose infusion, the ratios of (2)H to (14)C and of (3)H to (14)C in blood glucose were 30% less than in the galactose. (3)H at carbon 6 was 1% of that at carbon 1 of the glucose. Thus, although the two hydrogens bound to carbon 1 and the two bound to carbon 6 of fructose 6-phosphate (p) during gluconeogenesis are equally enriched in (2)H via pyruvate's equilibration with alanine, one of each is further enriched via hydration of fumarate that is converted to glucose. That hydrogen at carbon 1 of fructose 6-phosphate (P) is also enriched in fructose 6-P's equilibration with mannose 6-P. (2)H from (2)H(2)O at carbon 1 to carbon 2 of blood glucose cannot then quantitate gluconeogenesis because of [1-(2)H]glucose formation during glycogenolysis. Triose-P cycling has a minimal effect on quantitation. (2)H recovery in glucose from [1-(2)H]galactose does not quantitate galactose conversion via UDP-glucose to glycogen.
Adult↗
Contributions by kidney and liver to glucose production in the postabsorptive state and after 60 h of fasting.
Contributions of renal glucose production to whole-body glucose turnover were determined in healthy individuals by using the arteriovenous balance technique across the kidneys and the splanchnic area combined with intravenous infusion of [U-13C6]glucose, [3-(3)H]glucose, or [6-(3)H]glucose. In the postabsorptive state, the rate of glucose appearance was 11.5 +/- 0.6 micromol x kg(-1) x min(-1). Hepatic glucose production, calculated as the sum of net glucose output (9.8 +/- 0.8 micromol x kg(-1) x min(-1)) and splanchnic glucose uptake (2.2 +/- 0.3 micromol x kg(-1) x min(-1)) accounted for the entire rate of glucose appearance. There was no net exchange of glucose across the kidney and no significant renal extraction of labeled glucose. The renal contribution to total glucose production calculated from the arterial, hepatic, and renal venous 13C-enrichments (glucose M+6) was 5 +/- 2%. In the 60-h fasted state, the rate of glucose appearance was 8.2 +/- 0.3 micromol x kg(-1) x min(-1). Hepatic glucose production, estimated as net splanchnic output (5.8 +/- 0.7 micromol x kg(-1) x min(-1)) plus splanchnic uptake (0.6 +/- 0.3 micromol x kg(-1) x min(-1)) accounted for 79% of the rate of glucose appearance. There was a significant net renal output of glucose (0.9 +/- 0.3 micromol x kg(-1) x min(-1)), but no significant extraction of labeled glucose across the kidney. The renal contribution to whole-body glucose turnover calculated from the 13C-enrichments was 24 +/- 3%. We concluded that 1) glucose production by the human kidney in the postabsorptive state, in contrast to recent reports, makes at most only a minor contribution (approximately 5%) to blood glucose homeostasis, but that 2) after 60-h of fasting, renal glucose production may account for 20-25% of whole-body glucose turnover.
Adult↗
Glucose production and gluconeogenesis in adults with uncomplicated falciparum malaria.
Although glucose production is increased in severe malaria, the influence of uncomplicated malaria on glucose production is unknown. Therefore, we measured in eight adult Vietnamese patients with uncomplicated falciparum malaria and eight healthy Vietnamese controls glucose production (by infusion of [6,6-2H2]glucose) and the fractional contribution of gluconeogenesis (by oral ingestion of 2H2O); glycogenolysis was calculated as the difference between the two. After 20 h of fasting, plasma glucose was 4.7 +/- 0.2 mmol/l in the patients and 4.3 +/- 0.2 mmol/l in the controls (not significant). Glucose production was approximately 25% higher in the patients (16.9 +/- 1.3 vs. 13.4 +/- 0.3 mumol.kg-1.min-1, P = 0.01). Fractional and absolute gluconeogenesis were increased in the patients (approximately 87 vs. approximately 59%, P < 0.001; and 14.6 +/- 1.3 vs. 7.9 +/- 0.2 mumol.kg-1.min-1, P < 0.001, respectively). The contribution of glycogenolysis to total glucose production was decreased in the patients: 2.3 +/- 0.5 vs. 5.5 +/- 0.4 mumol.kg-1.min-1 (P < 0.002). In conclusion, in adult patients with uncomplicated falciparum malaria, glucose production is increased by approximately 25% due to an increased rate of gluconeogenesis, whereas glycogenolysis is decreased. The mechanism by which these changes occur is uncertain. However, counterregulatory hormone and cytokine concentrations were increased in the patients.
Adult↗
Quantifying gluconeogenesis during fasting.
The use of 2H2O in estimating gluconeogenesis' contribution to glucose production (%GNG) was examined during progressive fasting in three groups of healthy subjects. One group (n = 3) ingested 2H2O to a body water enrichment of approximately 0.35% 5 h into the fast. %GNG was determined at 2-h intervals from the ratio of the enrichments of the hydrogens at C-5 and C-2 of blood glucose, assayed in hexamethylenetetramine. %GNG increased from 40 +/- 8% at 10 h to 93 +/- 6% at 42 h. Another group ingested 2H2O over 2.25 h, beginning at 11 h (n = 7) and 19 h (n = 7) to achieve approximately 0.5% water enrichment. Enrichment in plasma water and at C-2 reached steady state approximately 1 h after completion of 2H2O ingestion. The C-5-to-C-2 ratio reached steady state by the completion of 2H2O ingestion. %GNG was 54 +/- 2% at 14 h and 64 +/- 2% at 22 h. A 3-h [6,6-2H2]glucose infusion was also begun to estimate glucose production from enrichments at C-6, again in hexamethylenetetramine. Glucose produced by gluconeogenesis was 0.99 +/- 0.06 mg.kg-1.min-1 at both 14 and 22 h. In a third group (n = 3) %GNG reached steady state approximately 2 h after 2H2O ingestion to only approximately 0.25% enrichment. In conclusion, %GNG by 2 h after 2H2O ingestion and glucose production using [6,6-2H2]glucose infusion, begun together, can be determined from hydrogen enrichments at blood glucose C-2, C-5, and C-6. %GNG increases gradually from the postabsorptive state to 42 h of fasting, without apparent change in the quantity of glucose produced by gluconeogenesis at 14 and 22 h.
Adult↗
Contributions of gluconeogenesis to glucose production in the fasted state.
Healthy subjects ingested 2H2O and after 14, 22, and 42 h of fasting the enrichments of deuterium in the hydrogens bound to carbons 2, 5, and 6 of blood glucose and in body water were determined. The hydrogens bound to the carbons were isolated in formaldehyde which was converted to hexamethylenetetramine for assay. Enrichment of the deuterium bound to carbon 5 of glucose to that in water or to carbon 2 directly equals the fraction of glucose formed by gluconeogenesis. The contribution of gluconeogenesis to glucose production was 47 +/- 49% after 14 h, 67 +/- 41% after 22 h, and 93 +/- 2% after 42 h of fasting. Glycerol's conversion to glucose is included in estimates using the enrichment at carbon 5, but not carbon 6. Equilibrations with water of the hydrogens bound to carbon 3 of pyruvate that become those bound to carbon 6 of glucose and of the hydrogen at carbon 2 of glucose produced via glycogenolysis are estimated from the enrichments to be approximately 80% complete. Thus, rates of gluconeogenesis can be determined without corrections required in other tracer methodologies. After an overnight fast gluconeogenesis accounts for approximately 50% and after 42 h of fasting for almost all of glucose production in healthy subjects.
Adult↗
Glycerol production and utilization in humans: sites and quantitation.
Liver is assumed to be the major site of glycerol uptake and fatty acid reesterification. [U-13C]glycerol was infused into ten 60 h-fasted healthy subjects. Measured were 1) blood glycerol concentrations and 13C enrichments in brachial and pulmonary arteries and in hepatic, renal, superficial, and deep forearm veins; 2) glycerol appearance rates in systemic circulation; and 3) splanchnic bed and kidney glycerol uptakes with use of balance and tracer methodology. Glycerol concentrations were one-fifth in hepatic, one-half in renal, 40% more in superficial, and the same in deep vein and pulmonary artery as in brachial artery blood. Glycerol enrichments were one-fifth in hepatic, two-thirds to three-quarters in renal and superficial veins, and the same in pulmonary as in brachial artery blood. Splanchnic glycerol uptake was 29% and kidney glycerol uptake was 17% of glycerol's rate of appearance, 5.11 mumol.min-1.kg-1. Splanchnic fatty acid uptake was 25% of calculated fatty acid release. Glycerol contributed 15% to glucose production. Most of the [13C]glycerol uptake by splanchnic bed and kidneys was incorporated into glucose. Thus, in 60 h-fasted individuals, most glycerol uptake does not occur in liver, and the extent of fatty acid reesterification in liver is in doubt.
Adult↗