| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Pediatric Endocrinology |
Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children’s Hospital, University of Pittsburgh; and the Department of Family Medicine and Clinical Epidemiology, Division of Biostatistics, University of Pittsburgh School of Medicine (J.E.J.), Pittsburgh, Pennsylvania 15213
Address all correspondence and requests for reprints to: Silva Arslanian, M.D., Division of Endocrinology, Children’s Hospital of Pittsburgh, 3705 Fifth Avenue at Desoto Street, Pittsburgh, Pennsylvania 15213.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Fasting and first phase insulin concentrations were higher in blacks than in whites [14.7 ± 1.3 vs. 10.4 ± 1.2 (P = 0.02) and 76.9 ± 6.8 vs. 52.1 ± 6.4 µU/mL (P = 0.016)]. There were no differences in second phase insulin levels and insulin sensitivity index. Both maximal oxygen consumption (VO2max) and resting energy expenditure were lower in black children, whereas insulin-like growth factor I was higher. After controlling for these differences, race contributed significantly to basal insulin, but not to first phase insulin.
In summary, previously reported black/white differences in insulin secretion and sensitivity during adolescence may have their origin in early childhood manifested as hyperinsulinemia. However, genetic (race) vs. environmental factors (physical activity/fitness and energy balance) should be carefully scrutinized as potential factors responsible for such differences.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Recently, we found that healthy black adolescents have lower insulin sensitivity and higher first and second phase insulin levels than white adolescents (6). The present studies were undertaken to determine whether black/white differences in insulin secretion and sensitivity are present in the prepubertal age group or are only detected during puberty. The latter is a developmental stage characterized by a temporary decrease in insulin sensitivity compensated for by increased insulin secretion (7, 8).
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
. All subjects
were documented to be in good health by history, physical examination,
and routine hematological and biochemical tests. None was receiving any
medications. None had a first degree relative with diabetes, and none
was a competitive athlete. Pubertal development was assessed by
physical examination according to the criteria of Tanner and confirmed
by measurements of plasma testosterone in males, estradiol in females,
and dehydroepiandrosterone sulfate in both (Table 1). All participants
were advised to follow a weight-maintaining diet containing 55%
carbohydrate, 30% fat, and 15% protein for 1 week before testing.
Testing was performed after a 12-h overnight fast (6).
|
First and second phase insulin secretions were assessed during a hyperglycemic clamp experiment. Plasma glucose was increased rapidly during a 2-min period to 225 mg/dL by bolus infusion of 25% dextrose and maintained at that level by variable rate infusion of 20% dextrose solution for 120 min. Glucose and insulin concentrations were measured every 2.5 min for the first 15 min and then every 15 min until the end of the 120-min clamp study (6).
Resting energy expenditure, carbon dioxide production, oxygen consumption, and respiratory quotient were measured by continuous indirect calorimetry (Deltatrac Medics, Yorba Linda, CA) over 30 min before the hyperglycemic clamp. The intraexperiment coefficients of variation for respiratory quotient, carbon dioxide production (VCO2), and maximal oxygen consumption (VO2) were less than 7% in each subject. Basal carbohydrate and lipid oxidation rates were calculated from gaseous exchange data, as described previously (6, 7).
Physical fitness, which is an important determinant of insulin sensitivity (9), was assessed in all participants. Maximal oxygen consumption (VO2max) was determined during progressive bicycle ergometry to exhaustion performed in the Cardiopulmonary Physiology Laboratory at Children’s Hospital of Pittsburgh. The participants were assigned randomly to have this evaluation either 18 h before or 6 h after the clamp. The evaluation followed Godfrey’s protocol (10) as described by us previously (9, 11).
Biochemical measurements
Plasma glucose was measured by the glucose oxidase method with a glucose analyzer (Yellow Springs Instrument Co., Yellow Springs, OH), and the insulin concentration was determined by RIA (7). Plasma free fatty acids were quantitated by an enzymatic colorimetric method with a Wako NEFA C test kit (Biochemical Diagnostics, Idgewood, NY). Insulin-like growth factor I (IGF-I) was measured by RIA after acid-ethanol extraction (Nichols Institute, San Juan Capistrano, CA). Cholesterol, high density lipoprotein, and triglyceride measurements were performed using Center for Disease Control protocols as reported previously (11).
The first phase insulin concentration was calculated as the mean of five determinations every 2.5 min during the first 15 min of the clamp experiment, and the second phase as the mean of eight determinations from 15–120 min. Insulin sensitivity was calculated by dividing the glucose disposal rate by the plasma insulin concentration during the last 60 min of the hyperglycemic clamp experiment as described previously (6).
Statistical analysis
Data are expressed as the mean ± SEM. Two-tailed Student’s t test compared the group of black vs. white subjects. Least squares linear regression analysis was applied to assess bivariate relationships. Nonparametric statistics were applied when analyzing data that had a skewed distribution. A nonparametric multiple regression model was used with ranking of all observed data to assess multivariate relationships. The goodness of fit of the model was measured by R2, the coefficient of determination, which is the square of multiple correlation coefficients between the dependent and independent variables (12, 13). Statistical significance was implied by P < 0.05.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
). Similarly,
plasma lipid profile was comparable between the two groups (Table 2).
|
).
Serum glucose concentrations at baseline and during the hyperglycemic
clamp were comparable between the two groups (Fig. 1).
Fasting and first phase insulin concentrations were significantly
higher in blacks than in whites (Fig. 1). The mean of three fasting
insulin concentrations every 15 min was 14.7 ± 1.3 µU/mL in
blacks and 10.4 ± 1.2 µU/mL in whites (P =
0.02). The first phase insulin concentration was 76.9 ± 6.8
µU/mL in blacks vs. 52.1 ± 6.4 µU/mL in whites
(P = 0.016). The second phase insulin concentration was
not significantly higher in blacks (89.7 ± 11.1 vs.
78.1 ± 8.5; P = 0.2; Fig. 1). Insulin sensitivity
was not significantly lower in blacks than in whites (17.4 ± 2.7
vs. 21.6 ± 2.8 mg/kg·min per µU/mL).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The first observation is the finding that basal and first phase insulin levels are higher in black prepubertal children than in their white peers during a hyperglycemic clamp. This finding is in agreement with the Bogalusa Heart Study of 377, 5- to 17-yr-old children and adolescents from a biracial black/white community, which showed higher insulin responses to an oral glucose tolerance test in blacks, especially females (14). The same researchers later reported that black children had higher fasting insulin levels and lower C peptide/insulin ratios, suggesting that elevated fasting insulin levels in blacks may be due to decreased insulin clearance and not increased secretion (15). However, careful studies to measure insulin clearance are needed before such conclusions are accepted. Similar findings of hyperinsulinemia were observed in black adults (16, 17). In the present study, once differences in VO2max are controlled for, the black/white difference in first phase insulin secretion disappears. There remains, however, a significant race effect on fasting insulin level despite adjusting for differences in physical fitness levels. The 40% higher fasting insulin levels in black children are unlikely to be due to higher fatness levels, because there was no significant difference in body mass index between the two groups. Similar to our findings, Gutin et al. found that 7- to 11-yr-old black children have higher fasting insulin levels than whites after adjusting for differences in fatness (18). It remains to be determined whether the higher fasting insulin level in black children is secondary to decreased hepatic clearance as proposed previously (15), is due to an up-regulation of basal insulin secretion, or is caused by a combination of both factors.
Black Americans are at increased risk of obesity, NIDDM, gestational diabetes, and cardiovascular disease mortality (1, 2). Despite this, the metabolic precursors that result in these morbidities remain unknown. At present, the controversy continues in regard to the initial defect in the natural history of NIDDM. One hypothesis proposes that the primary defect is insulin resistance with subsequent B cell exhaustion and hyperglycemia. The opponents of this theory argue that hyperinsulinemia is consistently an early feature of animal models of obesity, and NIDDM and appears to precede a measurable deterioration of insulin action (19, 20). Studies in high risk populations such as the Pima Indians, Nauruans, and Mexican Americans favor the former theory (3, 4, 5). On the other hand, early studies in blacks failed to demonstrate a major association of insulin resistance with elements of syndrome X (21). However, lately the ARIC study of 14,481 participants between 45–64 yr of age indicates that clustering of syndrome X abnormalities (diabetes, hypertriglyceridemia, low high density lipoprotein, and hypertension) with insulin and waist hip ratio is present in African-Americans (22). The majority of these studies have been performed in adults. It may be necessary that investigations regarding natural history and/or precursors of disease in high risk populations be carried out at a very early stage of life before adaptive mechanisms overshadow the primary defect. In this regard, our cross-sectional studies demonstrate that in prepubertal children, fasting hyperinsulinemia is the only black/white difference. In pubertal adolescents, however, insulin sensitivity is also lower in blacks, whereas insulin secretion is higher (6). Adolescence is characterized by temporary insulin resistance, which subsides after completion of pubertal maturation (7, 8). It is possible that the evolution of insulin resistance during puberty is uncovering subtle racial differences in insulin levels that manifest themselves only as fasting hyperinsulinemia early in childhood. These findings are comparable to those in Pima Indian children, who have higher fasting insulin concentrations than Caucasian children (23). As hyperinsulinemia predicts subsequent NIDDM in high risk populations, such data suggest that the susceptibility to NIDDM is manifest at a young age as fasting hyperinsulinemia. It has to be cautioned though that these are cross-sectional studies, and longitudinal observations are needed. Regarding the observed gender difference in insulin sensitivity in black children, body composition assessment is needed before any definitive conclusions are made. In our previous studies of white children, we found no gender differences in insulin sensitivity when data were expressed per metabolically active fat-free mass (7).
In the present study, VO2max was assessed because physical activity/fitness is an important determinant of insulin sensitivity (9). The results demonstrate that black children have lower physical fitness levels than white children matched for physical characteristics. We did not have an evaluation of physical activity in these children. However, our results are in agreement with a previous report in adults which showed that blacks have lower VO2max than whites despite comparable age, sex, body mass index, and physical activity levels (24). Data are almost nonexistent in the pediatric age group for aerobic performance differences between black and white children. Limited surrogate questionnaire data show that white adolescents in a school district near Pittsburgh reported more activity than blacks in the same school (25). Moreover, among high school students, more blacks than whites were found to be in poor physical fitness condition (26). It remains to be clarified whether for similar levels of physical activity black children have comparable or lower VO2max levels than their white peers.
Another finding of the present investigation is the lower resting energy expenditure in black children compared with whites. This is true whether the data are expressed as total kilocalories per 24 h or corrected for body weight (kilocalories per kg/24 h). Within the last year, two separate groups of investigators demonstrated that resting energy expenditure is lower in black than white prepubertal children (27) and prepubertal girls (28), but not in pubertal girls (28). These results are in accordance with our findings of lower resting energy expenditure in black prepubertal children, but not in pubertal adolescents, as reported previously (6). The resting energy expenditure in the present study correlated positively with VO2max (r = 0.62; P = 0.002). It remains questionable whether this association is merely a reflection of the relationship of higher fitness levels with higher lean body mass and consequently higher resting energy expenditure or is mediated through differences in the energy cost of physical activity. The observed differences in black/white resting energy expenditure could be genetically determined, as heredity plays a significant role in the various components of energy expenditure (29), or could be environmentally modulated, as resting energy expenditure is higher in subjects with high levels of exercise and physical fitness (30). The correlation of resting energy expenditure with VO2max would favor the latter theory. Regardless of the nature of the lower energy expenditure in black children (heredity vs. lifestyle), it will predispose them to obesity in the presence of excess energy intake (31). Free living energy balance studies are needed to investigate the black/white divergence in body weight that emerges during puberty (32, 33).
Last, but not least, is the unexpected finding that IGF-I levels are higher in black than in white children. It is well known that GH and IGF-I levels increase during puberty (34). It is unlikely, however, that the higher IGF-I levels in black children are secondary to puberty, because both by careful clinical staging of puberty and biochemical evaluation (testosterone, estradiol, and dehydroepiandrosterone sulfate), all children were prepubertal. A recent study of adult black vs. white men and women demonstrated that black men had greater GH secretion (35), and black women had higher IGF-I/IGF-binding protein-3 molar ratio (36). Our findings, in harmony with the adult literature, indicate that racial differences in IGF-I levels could be detected early in childhood. The higher IGF-I levels in black children could be a reflection of greater GH secretion. On the other hand, the higher insulin levels in black children could depress IGF-binding protein-1 levels through inhibitory regulation (37). Additional studies with measurements of IGF-binding proteins are needed to discern the cause(s) of the higher IGF-I levels in black prepubertal children.
In summary, prepubertal black children have higher fasting insulinemia than their white peers. However, during a hyperglycemic clamp, insulin secretion and sensitivity are not different between black and white children after adjusting for differences in physical fitness levels.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Received December 3, 1996.
Revised February 20, 1997.
Accepted March 5, 1997.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  P. B Higgins, J. R Fernandez, W T. Garvey, W. M Granger, and B. A Gower Entero-insular axis and postprandial insulin differences in African American and European American children Am. J. Clinical Nutrition, November 1, 2008; 88(5): 1277 - 1283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Dokken and T.-S. Tsao The Physiology of Body Weight Regulation: Are We Too Efficient for Our Own Good? Diabetes Spectr, July 1, 2007; 20(3): 166 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Goodman, S. R. Daniels, and L. M. Dolan Socioeconomic Disparities in Insulin Resistance: Results From the Princeton School District Study Psychosom Med, January 1, 2007; 69(1): 61 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Ford, C. Li, G. Imperatore, and S. Cook Age, Sex, and Ethnic Variations in Serum Insulin Concentrations Among U.S. Youth: Findings from the National Health and Nutrition Examination Survey 1999-2002 Diabetes Care, December 1, 2006; 29(12): 2605 - 2611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B Albu, A. J Kovera, L. Allen, M. Wainwright, E. Berk, N. Raja-Khan, I. Janumala, B. Burkey, S. Heshka, and D. Gallagher Independent association of insulin resistance with larger amounts of intermuscular adipose tissue and a greater acute insulin response to glucose in African American than in white nondiabetic women Am. J. Clinical Nutrition, December 1, 2005; 82(6): 1210 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Isganaitis and R. H. Lustig Fast Food, Central Nervous System Insulin Resistance, and Obesity Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2451 - 2462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R McDuffie, D. C Adler-Wailes, J. Elberg, E. N Steinberg, E. M Fallon, A. M Tershakovec, S. A Arslanian, J. P Delany, G. A Bray, and J. A Yanovski Prediction equations for resting energy expenditure in overweight and normal-weight black and white children Am. J. Clinical Nutrition, August 1, 2004; 80(2): 365 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Weill, S Vanderbecken, and P Froguel Understanding the rising incidence of type 2 diabetes in adolescence Arch. Dis. Child., June 1, 2004; 89(6): 502 - 504. [Full Text] [PDF]
|
|
|
|
|
|
D. J. Klein, L. Aronson Friedman, W. R. Harlan, B. A. Barton, G. B. Schreiber, R. M. Cohen, L. C. Harlan, and J. A. Morrison Obesity and the Development of Insulin Resistance and Impaired Fasting Glucose in Black and White Adolescent Girls: A longitudinal study Diabetes Care, February 1, 2004; 27(2): 378 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Gassner and S. E. Gitelman Case Study: Type 1 and Type 2, Too? Clin. Diabetes, July 1, 2003; 21(3): 140 - 141. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bacha, R. Saad, N. Gungor, J. Janosky, and S. A. Arslanian Obesity, Regional Fat Distribution, and Syndrome X in Obese Black Versus White Adolescents: Race Differential in Diabetogenic and Atherogenic Risk Factors J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2534 - 2540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Goran, G. D. C. Ball, and M. L. Cruz Obesity and Risk of Type 2 Diabetes and Cardiovascular Disease in Children and Adolescents J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1417 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Goran, K. Coronges, R. N. Bergman, M. L. Cruz, and B. A. Gower Influence of Family History of Type 2 Diabetes on Insulin Sensitivity in Prepubertal Children J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 192 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Denburg, M. E. Silfen, A. M. Manibo, D. Chin, L. S. Levine, M. Ferin, D. J. McMahon, C. Go, and S. E. Oberfield Insulin Sensitivity and the Insulin-Like Growth Factor System in Prepubertal Boys with Premature Adrenarche J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5604 - 5609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Goran, R. N. Bergman, M. L. Cruz, and R. Watanabe Insulin Resistance and Associated Compensatory Responses in African-American and Hispanic Children Diabetes Care, December 1, 2002; 25(12): 2184 - 2190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen and T. O. Scholl Ethnic Differences in C-Peptide/Insulin/Glucose Dynamics in Young Pregnant Women J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4642 - 4646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Arslanian, R. Saad, V. Lewy, K. Danadian, and J. Janosky Hyperinsulinemia in African-American Children: Decreased Insulin Clearance and Increased Insulin Secretion and Its Relationship to Insulin Sensitivity Diabetes, October 1, 2002; 51(10): 3014 - 3019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Salbe, C. Weyer, R. S. Lindsay, E. Ravussin, and P. A. Tataranni Assessing Risk Factors for Obesity Between Childhood and Adolescence: I. Birth Weight, Childhood Adiposity, Parental Obesity, Insulin, and Leptin Pediatrics, August 1, 2002; 110(2): 299 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Gower, W. M. Granger, F. Franklin, R. M. Shewchuk, and M. I. Goran Contribution of Insulin Secretion and Clearance to Glucose-Induced Insulin Concentration in African-American and Caucasian Children J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2218 - 2224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. B. Kaplowitz, E. J. Slora, R. C. Wasserman, S. E. Pedlow, and M. E. Herman-Giddens Earlier Onset of Puberty in Girls: Relation to Increased Body Mass Index and Race Pediatrics, August 1, 2001; 108(2): 347 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Danadian, V. Lewy, J. J. Janosky, and S. Arslanian Lipolysis in African-American Children: Is It a Metabolic Risk Factor Predisposing to Obesity? J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3022 - 3026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A Yanovski Resting energy expenditure in African American and white children Am. J. Clinical Nutrition, February 1, 2001; 73(2): 149 - 150. [Full Text] [PDF]
|
|
|
|
|
|
P. Vuguin, B. Linder, R. G. Rosenfeld, P. Saenger, and J. DiMartino-Nardi The Roles of Insulin Sensitivity, Insulin-Like Growth Factor I (IGF-I), and IGF-Binding Protein-1 and -3 in the Hyperandrogenism of African-American and Caribbean Hispanic Girls with Premature Adrenarche J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2037 - 2042. [Abstract] [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
