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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0626
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 8 4496-4502
Copyright © 2005 by The Endocrine Society

Effects of Dietary Macronutrient Intake on Insulin Sensitivity and Secretion and Glucose and Lipid Metabolism in Healthy, Obese Adolescents

Agneta L. Sunehag, Gianna Toffolo, Marco Campioni, Dennis M. Bier and Morey W. Haymond

Baylor College of Medicine (A.L.S., D.M.B., M.W.H.), Children’s Nutrition Research Center, Houston, Texas 77030; and Department of Electronics and Informatics (G.T., M.C.), University of Padua, 35131 Padua, Italy

Address all correspondence and requests for reprints to: Agneta L. Sunehag, M.D., Ph.D., Children’s Nutrition Research Center, 1100 Bates Street, Houston, Texas 77030. E-mail: asunehag{at}bcm.tmc.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: Adolescent obesity is a serious public health concern.

Objective: The aim of the study was to determine whether obese adolescents can adapt metabolically to changes in dietary macronutrient intake.

Patients and Design: Using a random cross-over design, 13 healthy obese volunteers (six boys and seven girls; age, 14.7 ± 0.3 yr; body mass index, 34 ± 1 kg/m2; body fat, 42 ± 1%) were studied twice after 7 d of isocaloric, isonitrogenous diets with 60% carbohydrate (CHO) and 25% fat (high CHO), or 30% CHO and 55% fat (low CHO).

Main Outcome Measures and Methods: Glucose metabolism, insulin sensitivity, and first- and second-phase insulin secretory indices were measured by stable isotope techniques and the stable labeled iv glucose tolerance test. The results were compared with those of previously studied lean adolescents.

Results: Obese adolescents increased first- and second-phase insulin secretory indices by 18 (P = 0.05) and 36% (P = 0.05), respectively, to maintain normoglycemia during the high-CHO diet because they failed to increase insulin sensitivity as did the lean adolescents. Regardless of diet, in obese adolescents, insulin sensitivity was half (P < 0.05) and first- and second-phase insulin secretory indices twice (P < 0.01), compared with the the corresponding values in lean subjects. In obese adolescents, gluconeogenesis increased by 32% during the low-CHO (high-fat diet) (P < 0.01).

Conclusion: In obese adolescents, insulin secretory demands were increased regardless of diet. Failure to increase insulin sensitivity while receiving a high-CHO diet required a further increase in insulin secretion, which may lead to earlier ß-cell failure. A low-CHO/high-fat diet resulted in increased gluconeogenesis, which may be a prelude to the increased glucose production and hyperglycemia observed in type 2 diabetics.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
OBESITY IN CHILDREN and adolescents is an increasingly serious public health concern. Over the past three decades, the prevalence of American children and adolescents (6–19 yr) with body mass index (BMI) greater than the 95th percentile for age has increased from 4–5 to 15% using standards that are based on height and weight data from 1963 to 1994 (1).

In addition, the overall prevalence of the metabolic syndrome among adolescents (12–19 yr) is approximately 4% (2), whereas among obese adolescents it is nearly 30% (2) and 50% among severely obese adolescents (3). Concomitant with the increase in childhood obesity, the proportion of type 2 diabetes has increased severalfold among children and adolescents with newly diagnosed diabetes (4, 5, 6, 7, 8); the vast majority is obese. Many factors have been attributed to the development of obesity in children and adolescents, e.g. parental obesity (including both genetic and environmental components) (9, 10), total energy intake, relative fat intake (11, 12, 13, 14), reduced energy expenditure, and decreased physical activity (4, 15, 16).

The impact of dietary macronutrient composition on insulin sensitivity and blood lipids has been extensively studied in adults of different ages (17, 18, 19, 20, 21, 22, 23). Chen et al. (17) reported that during ad libitum diet, elderly men (65–82 yr) were insulin resistant as compared with young men (18–36 yr). However, 3–5 d of a diet providing 85% CHO corrected their insulin resistance. In healthy subjects (14–61 yr) instructed to consume a low-fat/high-CHO diet for 3 months, low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio was reduced (the decrease in LDL cholesterol was 2.5 times that of HDL) (18). In contrast, in healthy middle-aged men and women (19) and postmenopausal women (20), increasing dietary CHO intake from 40 to 60% resulted in increased triglyceride concentrations. Several (but not all) studies have demonstrated increased insulin secretion and plasma lipid concentrations after high sucrose/fructose intake (21). On the other hand, high-fat/low-carbohydrate (CHO) diets have been associated with increased insulin resistance and increased number of risk factors for cardiovascular disease in healthy adult female and males within a wide age range (22, 23).

We previously demonstrated that lean adolescents readily adapt to substantial changes in dietary CHO and fat content by adjusting their substrate oxidation rates to match the macronutrient intakes (24). Furthermore, while on the high-CHO diet, lean subjects maintained normoglycemia by increasing insulin sensitivity without increasing insulin secretion (24). In addition, increasing the dietary fructose content from 10 to 40% of the CHO intake had no impact on glucose metabolism, insulin sensitivity, insulin secretion, or blood lipids in healthy lean adolescents (24). Although the impact of obesity on insulin sensitivity is well established in children and adolescents (25, 26, 27, 28), the impact of changes in macronutrient intake on metabolic adaptation in obese adolescents remains to be determined. Therefore, the present studies were undertaken to determine whether changes in dietary macronutrient intake affect insulin secretion and/or insulin sensitivity or glucose and lipid metabolism in healthy obese adolescents. We hypothesized that, regardless of diet, apparently healthy, obese adolescents are insulin resistant but maintain normal plasma concentrations of glucose and lipids by increasing insulin secretion and that they further increase insulin secretion to dispose of a high-CHO diet rather than increasing insulin sensitivity.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Experimental subjects

Obese adolescents. After approval of the protocol by the Baylor College of Medicine Institutional Review Board for Human Subject Research and obtaining assent from the subject and consent from the legal guardian, 13 subjects (six boys and seven girls) were recruited by local advertisement and studied. The subject characteristics are displayed in Table 1Go. In agreement with the inclusion criteria, the subjects ranged between 13 and 17 yr of age; were Tanner pubertal stage IV-V; had BMI above the 95th percentile for age; and a corresponding body fat content of more than 30% determined by dual-energy x-ray absorptiometry (Delphi-A, software version 11.1; Hologic, Bedford, MA). They were in good health as determined by a medical history, a physical examination, and standard blood chemistry analyses (including fasting blood glucose, lipids, liver enzymes, hemoglobin A1c, and hemoglobin/hematocrit); taking no medications including birth control pills; had regular menses; and had no first-degree relatives with diabetes. Attempts were made to recruit from all ethnic groups resulting in the following ethnic distribution: three European-Americans, eight Afro-American, and two Hispanic American.


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  		TABLE 1. Subject characteristics (mean ± SE)

 
Lean subjects (previously studied) (24). Healthy lean adolescents were studied previously using an identical protocol and methodology (24). The lean subjects differed from the obese only with regard to BMI (<26 kg/m2) and body fat content (<25%) (24).

Power calculations for the present study in obese subjects (as well as the previous in lean) were based on a previous study addressing the reproducibility of measurements of plasma concentrations of substrates and hormones, glucose and lipid kinetics, and insulin sensitivity and secretion in children and adolescents (29). Thus, with a paired study design, 12 subjects would allow us to detect 15–30% effects of changes in dietary macronutrient intake on all primary outcome variables.

Tracers

Sterile and pyrogen-free deuterium oxide (99 atom percent 2H), [2H5]glycerol (99 atom percent [2H]; 93.5% [2H5]), [1-13C]glucose (99 atom percent [13C]); and [6,6-2H2]glucose (99% [2H]; 98% [2H2]) were purchased from Cambridge Isotope Laboratories (Andover, MA). The isotopes were prepared as previously described (24).

Study design

The design, methods, and analyses used in the present study of obese adolescents are identical with those used in our previous study of lean children and adolescents (24). Briefly, the subjects were studied on two occasions separated by approximately 8 wk. The menstrual phase was not standardized in the studies of the girls because it is difficult to predict the menstrual periods in obese girls (even though girls with clear oligomenorrhea were excluded); the studies had to be scheduled in advance because each study was preceded by a 7-d diet period followed by 3 d of metabolic studies (see details below); and as an unavoidable, practical issue in school-aged children, the inpatient aspect of these studies were performed on weekends to avoid the subjects missing school days.

For the 7 d before each study occasion, the subjects were randomly assigned to receive either a low-CHO/high-fat diet (low CHO: 30% CHO, 55% fat, and 15% protein) or an isocaloric high-CHO/low-fat diet (high CHO: 60% CHO, 25% fat, and 15% protein). In both diets, the total fructose content (free fructose and fructose in sucrose) was maintained at 20% of the total CHO content. The designed diets were compounded using the Minnesota Database System (version 2.8 NDS, Minneapolis, MN) (24) that provides information about energy and macronutrient composition of a large number of common food items. Major components of the low-CHO/high-fat diet were, for example, sausages, bacon, potato chips, ice cream, whipped cream, butter, eggs, mayonnaise, and salads dressing, whereas the high-CHO/low-fat diet was based on pasta, rice, potatoes, bread, cookies, and fruit. Total energy intake was predicted from weight, age, and reported values of physical activity (30). Three meals and two snacks per day were weighed, prepacked, and sent to the subjects’ homes. Nonconsumed food was returned to the kitchen, examined for constituents, and the energy and macronutrient composition of the consumed food was calculated by difference using the Minnesota Database System (see Table 3Go) (24). A research dietitian was in almost daily telephone contact with the families to assure each child’s compliance with the diet.


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  		TABLE 3. Overnight fasting substrate and hormone concentrations in response to the low-CHO/high-fat and high-CHO/low-fat diets, respectively (mean ± SE)

 
Directly following each 7-d diet period at home, the subjects were admitted to the metabolic research unit (study d 1), and a 24-h calorimeter study was performed to assess energy expenditure and substrate oxidation rates (24, 31). During the calorimeter tests, the children were fed a diet with a composition equivalent to that of the week preceding the calorimetry study, except that total dietary energy intake was reduced by about 5% to adjust for a slightly lower activity level in the calorimeter. This was sufficient to achieve energy balance because the obese subjects were used to a sedentary lifestyle. After completion of the calorimetry study on the afternoon of study d 2, subjects were served dinner at 1700 h and a snack at 2000 h and were thereafter fasted (except for water) until termination of the inpatient study at 1300 h on d 3.

Administration of tracers

On each study occasion, the subjects received the following, stable isotopically labeled tracers as previously described (24).

Tracer 1. On study d 2 at 1000 h, 1200, 1400, 1600, and 1800 h, the subjects received five oral doses of deuterium oxide [a total of 3 g/kg lean body weight (166.7 mmol/kg lean body weight)] to measure gluconeogenesis (24).

Tracer 2. On study d 3, between 0600 and 1300 h, they received a simultaneous primed-constant rate iv infusion of [1-13C]glucose [3.58 mg/kg lean body weight (19.8 µmol/kg lean body weight); [0.06 ± 0.00 mg/kg lean body weight · min (0.33 ± 0.00 µmol/kg lean body weight · min)] and [2H5]glycerol [0.82 mg/kg lean body weight (8.4 µmol/kg lean body weight); 0.014 ± 0.000 mg/kg lean body weight · min (0.14 ± 0.00 µmol/kg lean body weight · min)] to measure rates of glucose production and glycerol turnover, respectively (24).

Tracer 3. At 0900 h on study d 3, after the 0 min blood sample (see below), a bolus injection of glucose, 0.35 ± 0.00 g/kg lean body weight (1.94 ± 0.00 mmol/kg lean body weight) containing 10% [6,6-2H2]glucose was administered over 90–120 sec in all children to measure peripheral insulin sensitivity and indices of first- and second-phase insulin secretion and glucose effectiveness (24). The deuterium enrichment in body water (after the ingestion of deuterium oxide described above) demonstrated that the plasma pool (mixing pool for glucose) is closely related to lean body mass. Because the lean body weight in the obese adolescents did not differ significantly from that of the previously studied lean subjects, adjusting the stable-label iv glucose tolerance test (SLIVGTT) glucose bolus to lean body weight rather than to total body weight resulted in a virtually identical glucose challenge in obese and lean adolescents (0.36 ± 0.01 g/kg lean body weight; 2.00 ± 0.06 mmol/kg lean body weight · min).

Blood sampling

Blood samples (5 ml each) were obtained at specific times beginning just before start of the period of continuous tracer infusion (see above), designated as t = –180 min. Subsequent samples were obtained at t = –30, –20, –10, and 0 min after which the SLIVGTT glucose bolus was injected and then at +2, 3, 4, 5, 8, 10, 18, 20, 28, 32, 40, 60, 120, 180, and 240 min (24, 32).

Analyses

Each blood sample was analyzed for substrate and hormone concentrations and tracer isotopic enrichments as previously described (24, 33). Visceral fat was measured by magnetic resonance imaging and fitness using a treadmill test as previously described (31).

Calculations

As we previously described in detail (24), plasma appearance rates of glucose (glucose production under fasting conditions) and glycerol (an indicator of lipolysis) were calculated under approximate steady-state conditions from the average enrichments obtained for [13C1]glucose and [2H3]glycerol, respectively, from –30 through 0 min. During the same period, the gluconeogenic contribution to glucose production was determined from the mean deuterium incorporation at glucose carbon 5 (24, 34).

Insulin sensitivity (the sensitivity of glucose disposition to insulin), first- and second-phase insulin secretory indices, and glucose effectiveness (the effect of glucose per se on its own disposition at basal insulin concentrations) were calculated using the stable labeled minimal model using the data obtained after the glucose bolus (24, 35, 36).

Statistical methods

Data are presented as mean ± SE. Differences between values obtained on the two study occasions were tested by paired, two-tailed t test. Differences between groups (obese vs. previously studied lean adolescents) were tested by one-way ANOVA followed by Fishers least significant differences test. Regression analysis was used to test the relationships between insulin sensitivity and visceral fat, respectively. P ≤ 0.05 was used to define statistical significance.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Subject characteristics are displayed in Table 1Go.

Energy intake and expenditure and substrate oxidation rates

Energy expenditure (EE) was not affected by diet and corresponded to the energy intake (EI): EE, 2,509 ± 110 (10,513 ± 467), and EI, 2,535 ± 95 kcal/d (10,622 ± 398 J/d) (low CHO); and EE, 2,471 ± 114 (10,354 ± 478), and EI, 2,483 ± 105 kcal/d (10,404 ± 440 J/d) (high CHO). Furthermore, the designed macronutrient composition of the intakes was achieved and substrate oxidation corresponded to the macronutrient distribution of the intakes (Table 2Go) during both diets. Nonprotein respiratory quotients were 0.83 ± 0.01 (low CHO) and 0.89 ± 0.01 (high CHO) (P < 0.001). Thus, as was observed in the previous study of lean adolescents (24), the obese adolescents adapted appropriately to changes in dietary CHO and fat intakes.


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  		TABLE 2. Macronutrient distribution of the intakes and substrate oxidation during the low-CHO/high-fat and high-CHO/low-fat diets, respectively (mean ± SE)

 
Baseline substrate and hormone concentrations

Blood glucose. Fasting blood glucose concentrations were not affected by dietary macronutrient intake (Table 3Go) and were identical with those reported previously in lean adolescents (24).

Plasma insulin and C-peptide concentrations. Fasting insulin and C-peptide concentrations were not affected by dietary macronutrient intake (Table 3Go) but demonstrate that obese subjects maintained normoglycemia at insulin and C-peptide concentrations 2–2.5 times those reported previously in lean adolescents (24).

Plasma adiponectin and C-reactive protein (CRP) concentrations. Data on adiponectin and CRP concentrations were not measured at the time of publication of the data on lean adolescents (24). Plasma concentrations of adiponectin and CRP were not affected by dietary macronutrient intake, but regardless of diet, obese adolescents had lower (P < 0.01) adiponectin and higher (P < 0.05) CRP concentrations than their lean counterparts (Table 4Go).


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  		TABLE 4. Overnight fasting plasma concentrations of adiponectin, CRP, cholesterol, and ß-OH butyrate in response to the low-CHO/high-fat and high-CHO/low-fat diets, respectively (mean ± SE)

 
Plasma lipids. Plasma concentrations of glycerol, triglycerides, and free fatty acids (FFA) were within normal range and were unaffected by dietary macronutrient intake (Table 3Go) and did not differ from those previously reported in lean adolescents (24). Total, HDL, and LDL cholesterol were maintained within normal range in both groups and were not affected by obesity, but during the low-CHO/high-fat diet, LDL cholesterol was higher in both obese and lean subjects (P < 0.05) (Table 4Go). Similarly, plasma ß-hydroxy butyrate (ß-OH butyrate) concentrations were also not affected by obesity but were higher after the low-CHO (high-fat) diet in both groups (P < 0.01 in obese and P < 0.05 in lean subjects) (Table 4Go) (cholesterol and ß-OH butyrate concentrations were not measured at the time of publication of the lean data (24).

Kinetic measurements

Glucose production from gluconeogenesis and glycogenolysis. Because data on glucose production from gluconeogenesis and glycogenolysis are central to this manuscript, previously published data on lean adolescents are included in Fig. 1Go for ease of comparison. When normalized to lean body weight, glucose production rates did not differ between obese and lean subjects regardless of diet (Fig. 1Go). However, during the low-CHO (high-fat) diet, gluconeogenesis increased by approximately 32% (P < 0.001) in the obese subjects but remained unchanged in the lean subjects (Fig. 1Go). Conversely, rates of glycogenolysis were reduced in response to the low-CHO (high-fat) diet in the obese subjects (Fig 1Go).



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  		FIG. 1. Rates of glucose production, gluconeogenesis, and glycogenolysis during the low- and high-CHO diets, respectively (mean ± SE). Gluconeogenesis is depicted in obese subjects by hatched bars and in lean subjects by solid black bars. Glycogenolysis is depicted by white solid bars in obese adolescents and gray solid bars in lean adolescents. Rate of glucose production is the sum of gluconeogenesis and glycogenolysis. During the low-CHO diet, gluconeogenesis was higher (P < 0.01) and glycogenolysis lower (P < 0.01) in obese compared with previously studied lean subjects (24 ). (Dividing the numbers in this figure by 0.18 will convert the data to micromoles per kilogram lean body weight per minute).

 
Lipolysis. Total plasma glycerol appearance rates (an indicator of lipolysis) were not affected by diet composition [21.5 ± 2.7 (234.1 ± 28.9) (low CHO) and 21.6 ± 3.0 mg/min (234.8 ± 32.6 µmol/min) (high CHO)] and did not differ from those previously reported in lean adolescents [22.3 ± 3.0 (242.2 ± 33.0), low CHO; and 22.1 ± 2.4 mg/min (239.9 ± 26.1 µmol/min), high CHO].

Insulin sensitivity, indices of insulin secretion, and glucose effectiveness

Because data on insulin sensitivity and secretion are central to this manuscript, previously published data on lean adolescents are included in Fig. 2Go for ease of comparison. During both diets, insulin sensitivity as measured by the SLIVGTT was reduced to approximately half (Fig. 2Go) and first- and second-phase insulin secretory indices were increased 2-fold in obese compared with lean adolescents (Fig. 2Go). Importantly, during the high-CHO diet challenge, the obese subjects were unable to increase insulin sensitivity but rather required an increase in insulin secretion to dispose of the received dietary CHO (Fig. 2Go). This response is in distinct contrast to that of the lean subjects who increased insulin sensitivity, but not insulin secretion, in response to the high-CHO diet (Fig. 2Go). Glucose effectiveness was not affected by dietary macronutrient intake but was slightly lower in the obese compared with the lean subjects (P < 0.05) (Fig. 2Go).



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  		FIG. 2. Insulin sensitivity, glucose effectiveness, and first- and second-phase insulin secretory indices during the low- and high-CHO diets, respectively, modeled by the SLIVGTT (mean ± SE). Hatched bars depict results obtained in obese adolescents, and solid bars depict results from previously studied lean subjects (24 ). a, P < 0.01; b, P < 0.05 (obese vs. lean).

 
Independent of total fat percent, visceral fat correlated inversely with insulin sensitivity: R = –0.57, P = 0.007 (low CHO); and R = –0.52, P = 0.015 (high CHO).


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
In agreement with previous reports (25, 26, 27, 28, 37), the healthy obese adolescents included in this study were highly insulin resistant, both in the overnight fasted state and in response to a glucose challenge (SLIVGTT). Importantly, however, our study also demonstrated that neither the fat nor the CHO composition of the diet had any effect on the degree of insulin resistance. Thus, to maintain normal glucose and lipid concentrations, normal rates of glucose production and lipolysis, and appropriate substrate oxidation, obese adolescents required a 2-fold increase in their insulin secretion. In addition, during the high-CHO diet, obese adolescents failed to increase insulin sensitivity (as was observed in their lean counterparts), requiring them to further increase insulin secretion. Over time this additional demand on pancreatic ß-cell function may contribute to early failure of the ß-cells and subsequent type 2 diabetes.

Obese adolescents maintained normal glucose production rates (i.e. not different from those obtained in lean adolescents), regardless of diet. However, during the low-CHO (high-fat) diet, the contribution from gluconeogenesis increased by 32% in obese but not lean adolescents. We interpret this as yet another consequence of the insulin-resistant state that becomes evident during the diminished CHO and increased fat ingestion. Increased gluconeogenesis after a high-fat diet has been reported in rats and was associated with hepatic fat accumulation (38, 39, 40) and in response to FFA administration in adult humans (41, 42). We did not measure liver fat in this study, but the observed association between a low-CHO (high-fat) diet and increased gluconeogenesis suggests that a high-fat diet could potentially increase the risk of fatty liver in obese adolescents. This issue needs further investigation.

The increase in gluconeogenesis with the low-CHO diet was compensated by a corresponding decrease in glycogenolysis, thus maintaining normal glucose production and suggesting that the obese subjects are capable of hepatic auto regulation (38) and that glycogenolysis may be more sensitive to insulin than gluconeogenesis (42, 43, 44). Because insulin secretion becomes limited over time, glucose production and subsequently blood glucose concentrations will increase as has been reported in type 2 diabetics (43, 45, 46).

Adiponectin, a cytokine released from adipose tissue, has been shown to be an indicator or a sensitizer of insulin sensitivity (47). Low adiponectin as well as high CRP concentrations are indicators of a state of inflammation and have been associated with increased risk of cardiovascular disease (48, 49). Our obese adolescents had significantly lower adiponectin and higher CRP concentrations, compared with their lean counterparts regardless of diet. Collectively the findings of insulin resistance, low adiponectin, and high CRP concentrations indicate that apparently healthy adolescents fulfilling only the obesity criteria of the metabolic syndrome are already at risk of type 2 diabetes and cardiovascular disease.

We conclude that in adolescents, the development of obesity itself is more important than the macronutrient composition of the diet in the context of insulin resistance and the resultant insulin hypersecretion. However, because obese adolescents were unable to improve insulin sensitivity in response to a high CHO intake, the latter diet led to a further increase in insulin secretion. These increased insulin secretory demands may lead to earlier ß-cell failure. On the other hand, in obese adolescents, a low-CHO (high-fat) intake led to increased gluconeogenesis, although normal glucose production was maintained by a compensatory reduction in glycogenolysis. These results demonstrate impaired metabolic flexibility in obese adolescents. Because when insulin secretion becomes inadequate to compensate for their insulin resistance, they become less able to appropriately dispose of a high-CHO diet and to suppress glycogenolysis during a low-CHO (high-fat) diet, and as a result either diet might lead to hyperglycemia.

Because long-term, well-controlled studies are difficult, if not impossible, to perform in an outpatient setting, we chose 7-d diet periods with pack-out meals and daily contact with the families and isocaloric and isonitrogenous diets with a significant difference with regard to CHO and fat content. Although we cannot predict long-term metabolic effects of dietary macronutrient composition, our data do not support the recommendations of either extremely high- or extremely low-CHO intakes in the management of obese adolescents but rather support focusing all efforts on reducing insulin resistance by preventing obesity in the first place, i.e. avoiding energy overconsumption.


   Acknowledgments
 
We thank our research nurses Amy Pontius and Andrea Dotting Jones, our dietitian Sandy Kattner, and the staff of the Metabolic Research Unit at the Children’s Nutrition Research Center for their invaluable help in conducting these studies; and we thank Lauren Loyal, Susan Sharma, Shaji Chacko, Dan Donaldson, Kathryn Louie, Cindy Clarke, Patricia Langley, Nancy Butte, and the calorimetry core laboratory staff, Dr. Chantal Rivera, Dr. Wayne Smith, and Dr.. Lynn Trautwein for excellent technical assistance.


   Footnotes
 
This work was supported by MARS, Inc., International Life Science Institute, and U.S. Department of Agriculture Cooperative Agreement 58-6250-6-001.

This work is a publication of the U.S. Department of Agriculture/Agricultural Research Service, Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine (Houston, Texas). The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement from the U.S. government.

First Published Online May 31, 2005

Abbreviations: BMI, Body mass index; CHO, carbohydrate; CRP, C-reactive protein; EE, energy expenditure; EI, energy intake; FFA, free fatty acids; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ß-OH butyrate, ß-hydroxy butyrate; SLIVGTT, stable-label iv glucose tolerance test.

Received March 22, 2005.

Accepted May 19, 2005.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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