| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Other Original Articles |
Department of Nutrition Sciences and Clinical Nutrition Research Center (B.A.G., F.F.), Department of Critical Care (W.M.G.), Department of Pediatrics (F.F.), and Department of Health Services Administration (R.M.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294-3360; and Departments of Preventive Medicine and Physiology and Biophysics, University of Southern California, and Institute for Prevention Research (M.I.G.), Los Angeles, California 90033
Address all correspondence and requests for reprints to: Dr. Barbara A. Gower, Department of Nutrition Sciences and Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294-3360. E-mail: . bgower{at}uab.edu
Abstract
Relative to Caucasians (C), African-American (AA) children and adults have lower indices of insulin sensitivity (Si) and a higher acute insulin response to glucose (AIRg). Among AA children, AIRg is greater than that which would be predicted based on lower Si. The objectives of the present study were 1) to determine whether insulin secretory parameters differ in AA vs. C children and adolescents using C-peptide modeling, 2) to determine whether hepatic insulin extraction differs with ethnicity/race using the C-peptide to insulin molar ratio, and 3) to determine whether the relatively greater AIRg among African-Americans is due to greater insulin secretion or lesser clearance. Subjects (n = 76) were AA and C children (mean age, 
11 yr). A 3-h tolbutamide-modified iv glucose tolerance test and minimal modeling were used to determine Si and AIRg. First phase C-peptide/insulin secretion and basal, first, and second phase ß-cell sensitivity to glucose were determined using C-peptide modeling with standard kinetic parameters developed in adults. The incremental C-peptide to insulin molar ratio over the 3-h test period, an index of hepatic insulin extraction, was calculated with the trapezoidal method. Si was lower and AIRg was higher in AA vs. C children. First phase C-peptide/insulin secretion and first phase ß-cell sensitivity to glucose were approximately 2-fold greater in AA vs. C children (P < 0.001); there were no between-group differences in basal or second phase ß-cell sensitivity to glucose. Hepatic insulin extraction was lower in AA vs. C (3.77 ± 1.78% vs. 5.99 ± 2.18%; P < 0.001). Multiple linear regression modeling indicated that first phase C-peptide/insulin secretion and hepatic insulin extraction contributed independently to AIRg; however, it was only first phase C-peptide/insulin secretion that explained the significant independent contribution of ethnicity/race to AIRg after adjusting for Si. The results of this study suggest that greater AIRg among AA is due to both greater insulin secretion and lesser hepatic insulin extraction, and that AIRg above that predicted based on lower Si is due to greater insulin secretion. The insulin secretion data await verification that the kinetic parameters used apply to children and AA.
THE ACUTE PHASE insulin concentration after a glucose challenge is greater among African-Americans (AA) compared with Caucasian-Americans (C) (1, 2, 3, 4, 5). Although this is attributed in part to ethnic/racial differences in insulin sensitivity (2, 3, 6, 7, 8) and associated compensatory mechanisms for maintaining hyperinsulinemia, the relative hyperinsulinemia among AA is greater than what would be expected based on differences in insulin sensitivity (9, 10). These observations imply that for any given degree of insulin sensitivity, either first phase insulin secretion is greater or hepatic insulin extraction is lesser among AA vs. C.
Differentiation of insulin secretion and clearance requires measurement of C-peptide. C-Peptide is secreted with insulin in equimolar amounts from the pancreas, but is not subject to hepatic extraction as is insulin and has a constant peripheral clearance. Thus, the relative amounts of C-peptide and insulin in the systemic circulation can be used to estimate hepatic insulin extraction (11). Insulin secretion can be estimated from mathematical modeling of C-peptide data during a frequently sampled iv glucose tolerance test. The minimal model of C-peptide kinetics proposed by Toffolo et al. (12) has been used to derive both an insulin secretion profile and several indices of ß-cell function. By incorporating glucose concentration throughout the test, indices of ß-cell sensitivity to glucose can be derived for basal, first phase, and second phase insulin secretion.
Few studies have used C-peptide measurements to address the possible physiological basis for the greater acute insulin response to glucose (AIRg) among AA. Among adult men and women, greater postchallenge insulin among AA was attributed to lower hepatic insulin extraction, as reflected in the lower molar ratio of C-peptide to insulin in AA vs. C during a glucose tolerance test (13). Among adolescents, AA were found to have lower hepatic insulin clearance, based on the ratio of fasting C-peptide to fasting insulin, but also lower, rather than higher, insulin secretion, based on the measurement of fasting C-peptide concentration (14). Using iv glucose tolerance testing with measurements of insulin and C-peptide throughout, obese adolescent AA were found to have lower insulin sensitivity and greater insulin secretion than age-, sex-, and pubertal stage-matched obese C children (5). None of these studies determined whether the insulin concentration was disproportionate to insulin sensitivity in AA. Thus, questions remain about the nature of the relatively greater AIRg among AA.
The objectives of the present study were 1) to determine whether insulin secretory parameters differ in AA vs. C children using C-peptide modeling, 2) to determine whether hepatic insulin extraction differs with ethnicity/race using the C-peptide to insulin molar ratio, and 3) to determine whether the greater AIRg among African-Americans [in excess of that predicted based on lower insulin sensitivity (Si)] is due to greater insulin secretion or lesser clearance.
Experimental Subjects
Subjects were 42 AA (19 males and 23 females) and 34 C (14 males and 20 females) children, aged 8–14 yr, who are taking part in an ongoing longitudinal study on body composition, body fat distribution, and disease risk factors. The present results were collected during the fall of 1999 and the winter/spring of 2000. All subjects were examined by a pediatrician, who determined pubertal status by the criteria of Tanner (15, 16). No child was taking medications known to affect body composition (e.g. ritalin or GH), had been diagnosed with syndromes or diseases known to affect body composition or fat distribution (e.g. Cushing’s, Down’s, or type 1 diabetes), or had been diagnosed with any major illness since birth. Ethnicity was determined by self-report. This study was approved by the institutional review board at University of Alabama at Birmingham, and parents provided informed consent before testing commenced.
Materials and Methods
Protocol
Subjects reported to the General Clinical Research Center (GCRC) at University of Alabama at Birmingham in the late afternoon for an overnight visit. They received a standard dinner and then fasted for 10–12 h until glucose tolerance testing the following morning. Body fat distribution was determined during the afternoon/evening of admission at the level of the umbilicus by single slice computed tomography scanning as previously described (8). Two weeks after the GCRC visit, body composition was determined at Department of Nutrition Sciences by dual energy x-ray absorptiometry (DPX-L, Lunar Corp., Madison, WI), as previously described (8).
Frequently sampled, iv glucose tolerance test (FSIGT)
At approximately 0600 h on the morning after GCRC admission, a topical anesthetic (Emla cream, AstraZeneca, Wilmington, DE) was applied to the antecubital space of both arms, and flexible iv catheters were placed. At time zero, glucose (25% dextrose; 11.4 g/m2) was administered iv. Blood samples (2.0 ml) were collected at the following times relative to glucose administration at 0 min: -15, -5, -1, 2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 25, 30, 40, 50, 70, 100, 140, and 180 min. Tolbutamide (125 mg/m2) was injected iv at 20 min. Sera were analyzed for glucose, insulin, and C-peptide.
Assays
Glucose was measured in 10 µl sera using an Ektachem DT II System (Johnson \|[amp ]\| Johnson, Rochester, NY). In our laboratory this analysis has a mean intraassay coefficient of variation (CV) of 0.61%, and a mean interassay CV of 1.45%. Insulin was assayed in duplicate 200-µl aliquots with a solid phase RIA (Diagnostic Products, Los Angeles, CA). In our laboratory this assay has a sensitivity of 11.4 pmol/liter, a mean intraassay CV of 5%, and a mean interassay CV of 6%. C-Peptide was measured in duplicate 25-µl aliquots with a double antibody RIA (Diagnostic Products). In our laboratory this assay has a sensitivity of 0.318 ng/ml, a mean intraassay CV of 3.57%, and a mean interassay CV of 5.59%.
Determination of insulin sensitivity and ß-cell function
Glucose and insulin values were entered into the MINMOD computer program (version 3.0, Richard N. Bergman) for determination of Si and AIRg 17, 18, 19). First phase C-peptide/insulin secretion and basal, first phase, and second phase ß-cell sensitivity to glucose were determined using the modeling equations reported by Toffolo et al. (12). First phase ß-cell sensitivity to glucose is equal to first phase C-peptide/insulin secretion divided by the maximum increment in the serum glucose concentration. Thus, first phase ß-cell sensitivity to glucose reflects the amount of hormone secreted normalized for the glucose load. Equations were programmed with SCIENTIST for Windows software (MicroMath Research, Salt Lake City, UT). The model rate constants were calculated based on age and obesity status using the regression equations of Van Cauter et al. (20) developed for adults. The model was fit to the C-peptide data with glucose as the forcing function, using the least squares algorithm and equal weighting for all data points. The C-peptide to insulin molar ratio was calculated using the incremental area under the curve (trapezoidal method) throughout the 180-min test period for each hormone as an index of hepatic insulin extraction. The highest C-peptide value measured for each subject during the first phase was used as peak first phase C-peptide concentration.
Statistical analyses
For all analyses variables were log-transformed to ensure normality of distribution. Two-way ANOVA, with ethnicity/race and gender as the class variables, was used to examine subject characteristics, derived variables from the FSIGT and minimal model, indices of ß-cell function, and the C-peptide to insulin molar ratio. Multiple linear regression analysis was used to identify variables independently associated with AIRg. The independent variables entered were ethnicity/race, those relevant variables that differed or tended to differ with ethnicity/race (Si, Tanner stage, lean mass, and visceral fat), and indices of insulin secretion and clearance. A series of six models was conducted, with independent variables added sequentially to illustrate their relative contributions. Analysis of covariance (ANCOVA) was used to generate adjusted means for AIRg. Due to a significant between-group difference in Tanner stage, analyses also were performed in a subset of the cohort group-matched for age and Tanner stage (n = 50; 27 AA and 23 C). ANOVA and regression modeling were conducted with SAS version 6.12 (SAS Institute, Inc., Cary, NC). Differences or effects were considered significant at P < 0.05.
Results
Descriptive data are shown in Table 1
. The ethnicity/race term was not significant in two-way ANOVA models for age, fat mass, body weight, body mass index, or sc abdominal fat, but was significant for Tanner stage (AA > C). In addition, AA subjects tended to have greater lean body mass (P = 0.08) and less visceral fat (P = 0.08) than C subjects. The gender term was significant for Tanner stage (girls > boys). Computed tomography scan information (visceral fat and sc abdominal fat) was not available for five subjects (one AA male, two AA females, one C male, and one C female). According to the most recent data available on obesity classification in children (21), 24% of the AA children were obese, and 26% of the C children were obese.
|
. Gender was not significant in any model; thus, data are shown by ethnicity/race. Si was lower (P < 0.01), and AIRg was greater (P < 0.001) in AA vs. C. Greater AIRg among AA was significant even after statistically adjusting for Si (P < 0.001; Fig. 1). Examination of fit indices from the C-peptide model showed that the mean coefficient of determination was 0.82 (range, 0.68–0.97), the mean correlation (between observed and calculated) was 0.91 (range, 0.83–0.96), and the mean r2 was 0.97 (range, 0.91–0.99). First phase C-peptide/insulin secretion and first phase ß-cell sensitivity to glucose were greater in AA vs. C (P < 0.001); there was no between-group difference in basal ß-cell sensitivity to glucose or second phase ß-cell sensitivity to glucose. The C-peptide to insulin molar ratio was greater in C (P < 0.001). Plots of mean glucose, C-peptide, and insulin concentrations during the FSIGT are shown in Fig. 2, A, B, and C, respectively. When expressed as the area under the curve for the entire 180-min test, glucose was significantly lower in AA vs. C (P < 0.01). The peak C-peptide concentration during the first phase was significantly higher in AA vs. C (P < 0.001).
|
|
|
), it was shown first that, as expected, AIRg was strongly related to Si (model 1). Subsequently, it was determined that ethnicity/race was independently associated with AIRg after adjusting for Si (model 2) and for Si, Tanner stage, lean mass, and visceral fat (model 3). However, adding the additional variable first phase C-peptide/insulin secretion eliminated the independent relationship between ethnicity/race and AIRg (model 4, Fig. 3). Although independently related to AIRg, hepatic insulin extraction did not eliminate the significant contribution of ethnicity/race (model 5). When both first phase C-peptide/insulin secretion and hepatic insulin extraction were in the model, both contributed independently to AIRg (model 6). Results did not differ if AA subjects with AIRg greater than 2 SD above the mean (four individuals) were eliminated from the analyses.
|
|
). Multiple linear regression analysis for the dependent variable AIRg indicated that ethnicity/race was no longer a significant determinant when Si, lean mass, visceral fat, and first phase C-peptide/insulin secretion were placed in the model (Table 5) or when Si, lean mass, visceral fat, first phase C-peptide/insulin secretion, and hepatic insulin extraction were in the model; these results agree with those obtained with the complete cohort.
|
|
The present study was conducted to determine whether insulin secretion or hepatic insulin extraction differed in AA vs. C children, and whether differences in insulin secretion, extraction, or both explained the higher absolute and Si-adjusted AIRg among AA. The C-peptide modeling results suggested that both first phase C-peptide/insulin secretion and ß-cell sensitivity to glucose were higher among AA; however, these results were derived using adult C-peptide kinetic parameters and need to be verified. In contrast, hepatic insulin extraction, determined from the C-peptide to insulin molar ratio, was lower among AA. Thus, the greater AIRg among AA may have been due to both greater insulin secretion and lesser insulin clearance. Multiple regression analysis suggested that greater AIRg in AA, after adjusting for Si, was due to greater insulin secretion.
Previous studies have shown that postglucose challenge insulin concentrations are higher among AA vs. C individuals (1, 2, 3, 5). This is true in adults, adolescents, and children. Although AA are also more insulin resistant (2, 3, 6, 7, 8), the relative hyperinsulinemia among AA is apparent in prepubertal children even after adjusting for Si (9, 10). Likewise, in the present study scatterplots of AIRg vs. Si clearly reveal that at any given degree of Si, AA have greater AIRg.
The source of greater AIRg among AA could be either greater insulin secretion or lesser hepatic insulin extraction. Results from C-peptide modeling suggested that both first phase C-peptide/insulin secretion and first phase ß-cell sensitivity to glucose were higher among AA. First phase C-peptide/insulin secretion presumably reflects the quantity of insulin that is synthesized and transported into a pool of hormone that is released immediately upon stimulation by glucose. First phase ß-cell sensitivity to glucose reflects the amount of hormone secreted normalized for the glucose load. The present results suggest that the pancreas in an AA subject is synthesizing and storing more insulin in an immediately available pool, and that this larger amount of hormone is released in response to a uniform glucose stimulus. For this reason, the AA group appears to have a greater first phase sensitivity to glucose.
We also examined the contribution of hepatic insulin extraction to AIRg, using the molar ratio of C-peptide to insulin throughout the 180-min FSIGT as an index of hepatic insulin extraction. Concern has been raised that the use of this ratio can lead to misinterpretation of data due to differences in the circulatory half-life and distribution space of the two hormones (11). However, after 180 min both C-peptide and insulin have returned to baseline concentrations. Thus, the ratio of C-peptide to insulin incremental area under the curve over the 180-min test period may be a reasonable reflection of hepatic insulin extraction (11). Lower hepatic insulin extraction appears to be responsible for greater AIRg among AA vs. C adults (13).
Similarly, the present results suggested that hepatic insulin extraction was approximately 37% lower in the AA vs. C children. Thus, a lesser degree of hepatic insulin extraction probably contributed to the greater AIRg in the AA group. The reason for lower hepatic insulin extraction among AA vs. C children is not known. Truncal lean body mass, as determined by dual energy x-ray absorptiometry, is 12.2% lower in AA vs. C, suggesting that organ mass may be lower in the former (22). It has been suggested that liver mass plays a significant role in determining the quantity of insulin extracted by the liver (23). Therefore, lower liver mass among AA vs. C may contribute to less hepatic insulin extraction.
Results from multiple regression modeling indicated that both insulin secretion and hepatic insulin extraction were significant independent determinants of AIRg in this group of children. However, when both first phase C-peptide/insulin secretion and hepatic insulin extraction were sequentially placed in a model for AIRg, only first phase C-peptide/insulin secretion eliminated the significant contribution of ethnicity/race to the model, after adjusting for Si. Thus, the relatively greater AIRg among AA (AIRg adjusted for Si) appeared to be due to greater insulin secretion.
In the present study Tanner stage did not play a role in determining AIRg. Although Tanner stage was placed in the regression models to account for the difference in Tanner stage between the two ethnic/racial groups, Tanner stage was not independently related to AIRg in any of the models. In addition, the data analyzed with the subset of children matched for Tanner stage produced results similar to those obtained with the entire sample. Thus, although Si decreases transiently during midpuberty (24, 25), this change did not influence the determinants of the ethnic/racial difference in AIRg investigated in this study.
The physiological significance of greater AIRg among AA children is unclear. Impaired, rather than excessive, first phase insulin secretion is associated with subsequent development of glucose intolerance and type 2 diabetes (26). Thus, AA children would eventually have to experience a decline in ß-cell function for the disease to develop. Higher AIRg among AA could result in a more rapid rate of glucose disposal and may be responsible for the lower glucose AUC observed among AA in the present study. In addition, greater glucose-stimulated insulin concentrations among AA and C children are inversely associated with circulating free fatty acids, suggesting that hyperinsulinemia among AA suppresses lipolysis (27), which is lower among AA children (28). Chronically suppressed lipolysis may contribute to lower circulating triglycerides among AA vs. C (29). Whether insulin-mediated suppression of lipid mobilization contributes to greater obesity among AA (30) remains to be determined.
A limitation of this study is the use of C-peptide kinetic parameters that were developed for C adults; similar kinetic data are not available for AA or for children. It is possible that renal clearance of C-peptide differs with ethnicity/race or age. Thus, there is risk in assuming that the published kinetic data apply to this study population, and results regarding insulin secretion should be considered tentative.
In conclusion, the present results suggest that greater AIRg among AA is due to both greater insulin secretion and lesser hepatic insulin extraction, and that AIRg above that predicted based on Si is due to greater insulin secretion. These results warrant confirmation with more robust indices of hepatic insulin extraction, e.g. indices obtained by mathematical modeling (31), and the use of ethnicity/race- and child- specific C-peptide kinetic parameters. Longitudinal studies are needed to determine whether and how greater AIRg early in life is related to risk for development of type 2 diabetes among AA.
Acknowledgments
The assistance of study coordinator Tena Hilario and the staff of the GCRC and the participation of the children and their families are gratefully acknowledged.
Footnotes
This work was supported by NICHHD Grants R29-HD-32668 and R01-HD/HL-33064 (to M.I.G.), NIDDK Grant R01-DK-58278 (to B.A.G.), Clinical Nutrition Research Center Grant P30-DK-56336, and General Clinical Research Center Grant M01-RR-00032.
Abbreviations: AA, African-American; AIRg, acute insulin response to glucose; ANCOVA, analysis of covariance; C, Caucasian; CV, coefficient of variation; FSIGT, frequently sampled, iv glucose tolerance test; GCRC, General Clinical Research Center; Si, insulin sensitivity.
Received September 24, 2001.
Accepted January 18, 2002.
References
This article has been cited by other articles:
 |
|
 |
|
  S. F. Burns, S. Lee, and S. A. Arslanian In Vivo Insulin Sensitivity and Lipoprotein Particle Size and Concentration in Black and White Children Diabetes Care, November 1, 2009; 32(11): 2087 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A Alvarez, P. B Higgins, R. A Oster, J. R Fernandez, B. E Darnell, and B. A Gower Fasting and postprandial markers of inflammation in lean and overweight children Am. J. Clinical Nutrition, April 1, 2009; 89(4): 1138 - 1144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Sam, A. D. Coviello, Y.-A. Sung, R. S. Legro, and A. Dunaif Metabolic Phenotype in the Brothers of Women with Polycystic Ovary Syndrome Diabetes Care, June 1, 2008; 31(6): 1237 - 1241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Velasquez-Mieyer, P. A. Cowan, S. Perez-Faustinelli, R. Nieto-Martinez, C. Villegas-Barreto, E. A. Tolley, R. H. Lustig, and B. S. Alpert Racial Disparity in Glucagon-Like Peptide 1 and Inflammation Markers Among Severely Obese Adolescents Diabetes Care, April 1, 2008; 31(4): 770 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Willemsen, S. W. K. de Kort, D. C. M. van der Kaay, and A. C. S. Hokken-Koelega Independent Effects of Prematurity on Metabolic and Cardiovascular Risk Factors in Short Small-for-Gestational-Age Children J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 452 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Rasouli, H. J. Spencer, A. A. Rashidi, and S. C. Elbein Impact of Family History of Diabetes and Ethnicity on -Cell Function in Obese, Glucose-Tolerant Individuals J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4656 - 4663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Kim, M. Ellmerer, E. L. Kirkman, and R. N. Bergman beta-Cell "rest" accompanies reduced first-pass hepatic insulin extraction in the insulin-resistant, fat-fed canine model Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1581 - E1589. [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]
|
|
|
|
|
|
A. Brehm, K. Thomaseth, E. Bernroider, P. Nowotny, W. Waldhausl, G. Pacini, and M. Roden The Role of Endocrine Counterregulation for Estimating Insulin Sensitivity from Intravenous Glucose Tolerance Tests J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2272 - 2278. [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]
|
|
|
|
 |
|
 N. C. Bush, B. E. Darnell, R. A. Oster, M. I. Goran, and B. A. Gower Adiponectin Is Lower Among African Americans and Is Independently Related to Insulin Sensitivity in Children and Adolescents Diabetes, September 1, 2005; 54(9): 2772 - 2778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ten and N. Maclaren Insulin Resistance Syndrome in Children J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2526 - 2539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Conwell, S. G. Trost, W. J. Brown, and J. A. Batch Indexes of Insulin Resistance and Secretion in Obese Children and Adolescents: A validation study Diabetes Care, February 1, 2004; 27(2): 314 - 319. [Abstract] [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]
|
|
|
|
|
|
X. Chen, T. O. Scholl, M. J. Leskiw, M. R. Donaldson, and T. P. Stein Association of Glutathione Peroxidase Activity with Insulin Resistance and Dietary Fat Intake during Normal Pregnancy J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5963 - 5968. [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]
|
|
|
|
|
|
B. A. Gower, J. R. Fernandez, T. M. Beasley, M. D. Shriver, and M. I. Goran Using Genetic Admixture to Explain Racial Differences in Insulin-Related Phenotypes Diabetes, April 1, 2003; 52(4): 1047 - 1051. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
) subjects (P < 0.001 for difference between groups, by ANCOVA).
) and C (
) subjects. All means are adjusted for Tanner stage, lean mass, and visceral fat. In addition, means in A are adjusted for Si, means in B are adjusted for Si and first phase C-peptide/insulin secretion, and means in C are adjusted for Si and hepatic insulin extraction. ***, P < 0.001 for difference between groups (by ANCOVA).