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(Circulation. 1997;96:4319-4325.)
© 1997 American Heart Association, Inc.

Articles

Summary Measures of the Insulin Resistance Syndrome Are Adverse Among Mexican-American Versus Non-Hispanic White Children

The Corpus Christi Child Heart Study

Lyn Steffen Batey, MPH; RD; David C. Goff, Jr, MD, PhD; Susan R. Tortolero, PhD; Milton Z. Nichaman, MD, ScD; Wenyaw Chan, PhD; Frances A. Chan, MS; JoAnne Grunbaum; EdD; Craig L. Hanis, PhD; ; Darwin R. Labarthe, MD, PhD

From the Southwest Center for Prevention Research; School of Public Health; University of Texas Houston Health Science Center; Houston.

Correspondence to Lyn Steffen Batey, MPH, RD, University of Texas Houston Health Science Center, School of Public Health, 1200 Herman Pressler Blvd, Houston, TX 77030. E-mail lsteffen{at}utsph.sph.uth.tmc.edu

	Abstract

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Background Mexican-American (MA) adults are known to have a greater burden of diabetes and insulin resistance than non-Hispanic white (NHW) people. In this report, we examined data obtained from MA and NHW third-grade children for evidence of a pattern consistent with the insulin resistance syndrome. In addition, we developed two summary measures characterizing insulin resistance syndrome to compare measures of this syndrome among our population.

Methods and Results Data regarding fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and body mass index (BMI) were available for 403 third-grade children. Median levels of insulin and glucose were significantly higher in MA boys and girls than in NHW boys and girls. Risk factors characterizing insulin resistance, including levels of insulin, triglycerides, systolic blood pressure, HDL cholesterol, and BMI were categorized as above or below the total population median. MA children were more likely than NHW children to have three or more adverse risk factors (55% versus 37%). When risk factors were converted to Z scores, and the five Z scores were summed for each individual, MA boys and girls had higher mean scores than NHW boys and girls (means for boys, 0.65 versus -0.97, P<.0001; girls, 0.52 versus -0.30, P<.04). Principal components analysis was used to create a summary score or index representing the insulin resistance syndrome. This summary score was significantly higher among MA boys and girls than NHW boys and girls (means for boys, 0.34 versus -0.72, P<.0001; girls, 0.35 versus -0.04, P=.056).

Conclusions Our results support the hypothesis that MA children exhibit a greater degree of the insulin resistance syndrome than NHW children, especially among boys. We conclude that some of the factors responsible for the increased risk of NIDDM seen among MA adults are demonstrable in childhood.

Key Words: risk factors • insulin • caronary disease

	Introduction

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Insulin resistance has been identified by several investigators as the disturbance underlying a cluster of metabolic abnormalities variously designated as syndrome X,¹ the deadly quartet,² the metabolic syndrome,^3–5 the insulin resistance syndrome,^6–8 the metabolic cardiovascular syndrome,⁹ or the atherothrombogenic syndrome.¹⁰ Several of these metabolic abnormalities are known risk factors for NIDDM and atherosclerosis, including hyperinsulinemia, hypertriglyceridemia, high blood pressure, low levels of HDL cholesterol, and obesity. Although obesity is not an essential component of the insulin resistance syndrome, it has been shown to modulate insulin resistance¹¹ and is usually included as a component of this syndrome. Individuals who have both insulin resistance and compensatory hyperinsulinemia are known to have hypertriglyceridemia and low levels of HDL cholesterol, high blood pressure, and possibly NIDDM and CHD.^12–15 In a population-based cohort of Mexican-American and non-Hispanic white adults, Haffner et al⁶ observed that those with higher levels of fasting insulin at baseline had an increased incidence of hypertriglyceridemia, low HDL cholesterol levels, NIDDM, and hypertension after 8 years of follow-up. This finding supports the idea that hyperinsulinemia and insulin resistance precede these risk factors and conditions in some individuals.

Mexican-American adults have a greater burden of NIDDM, hyperinsulinemia, and insulin resistance than non-Hispanic whites independent of obesity or age,^16–19 as well as higher CHD mortality rates.^20,21 According to the 1982 to 1984 Hispanic Health and Nutrition Examination Survey, Mexican-American adults have a high prevalence of NIDDM, which is two to three times that found in non-Hispanic whites.^22,23 Incidence data from the San Antonio Heart Study have demonstrated an earlier age of onset of NIDDM in the Mexican-American population.²⁴ The higher prevalence and earlier onset of NIDDM may be due to genetic factors among Mexican-Americans that predispose this population to a higher risk of developing NIDDM and consequently its complications.²⁵

There is increasing evidence that hyperinsulinemia, a marker for insulin resistance,²⁶ and insulin resistance itself may exist many years before the development of NIDDM, CHD, and other metabolic abnormalities.^27–30 Haffner et al³¹ observed that Mexican-American and non-Hispanic white adults who were identified as having an atherogenic pattern of risk factors at baseline were at greater risk for the subsequent development of diabetes. In another study, Haffner and colleagues³² found diminished insulin sensitivity and increased insulin response among nonobese, normoglycemic Mexican-American young adults compared with non-Hispanic whites, providing evidence that insulin resistance and hyperinsulinemia begin at a young age in Mexican Americans.³² Furthermore, several investigators have observed hyperinsulinemia and/or impaired glucose tolerance among populations of young Pima Indian, Papuan, Nauruan, and African- and Mexican-American children and adolescents.^27,33–35 Stuart and coworkers³⁵ observed a strong positive correlation between severity of acanthosis nigricans and levels of fasting insulin among African- and Mexican-American children. Because there are no published studies that have investigated the cluster of metabolic abnormalities representing insulin resistance in Mexican-American children, we undertook a study among third-grade Mexican-American and non-Hispanic white children to determine the distributions and patterns of association among the risk factors characterizing the insulin resistance syndrome: high insulin and triglyceride levels, high blood pressure, low HDL cholesterol concentrations, and obesity.

	Methods

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Population
The Corpus Christi Child Heart Study was designed as a cross-sectional survey of third-grade Mexican-American and non-Hispanic white children enrolled in the Corpus Christi (Texas) Independent School District during 1992 to 93. That district is located in Nueces County on the Texas gulf coast, where >90% of the children attend public school. The estimated population of Nueces County in the 1990 census was 291 145, of which 45% were non-Hispanic white, 51% were Hispanic (of these, 95% were Mexican American), and the remaining were African American, Asian American, and Native American. Eight elementary schools were selected to provide at least 300 Mexican-American and 300 non-Hispanic white children for the study. We attempted to recruit all third-grade children in each chosen school and enroll at least 125 children in each of four sex-ethnic groups. Among the 785 third-grade children recruited in the eight schools, 754 were Mexican American or non-Hispanic white and therefore eligible to participate in the study. As Fig 1 shows, 584 (77%) returned the parent questionnaire, and 498 (66%) participated in the screening visit. Exclusions from the analysis included 12 participants who were nonfasting at the time of examination and 83 with incomplete information. Participation did not vary by sex or ethnic group. The final study population for this analysis consisted of 102 and 107 Mexican-American boys and girls and 94 and 100 non-Hispanic white boys and girls, respectively, for a total of 403 (53%) children.

View larger version (21K): [in this window] [in a new window]   Figure 1. Recruitment of third-grade Mexican-American and non-Hispanic white study participants: the Corpus Christi Child Heart Study, 1994.

Data Collection
Recruitment began in the classrooms with presentations by study personnel about heart attack, stroke, cholesterol, diabetes, and blood pressure. The study was explained to the students, including the planned procedures and measurements and the fact that this was a voluntary project. Information packets for all third-grade students in the selected schools included a letter describing the study, the parental questionnaire addressing demography and family history, and consent forms. Spanish translations were included within each form. Teachers distributed the packets 2 weeks before data collection. Students were instructed to return the completed consent forms and questionnaire within 1 week. Study personnel scheduled meetings at the schools to explain the study procedures further and answer parents' questions. Each child who returned the completed forms was scheduled for a screening visit. Arrangements were made with the school cafeterias to provide study participants with breakfast after venipuncture, because children were to fast overnight.

Data collectors were trained and certified to measure height, weight, and blood pressure according to a standard protocol. Driscoll Children's Hospital provided the phlebotomy personnel. An examination was scheduled in the morning after an overnight fast. First, after a 5-minute rest, blood pressure was measured twice on the right arm of the seated child with a mercury sphygmomanometer. The mean values of each pair of blood pressure measurements for systolic and fourth- and fifth-phase diastolic pressure, respectively, were used to define an individual's blood pressure values. Height was measured to the nearest 0.1 cm by use of a portable stadiometer, and weight was measured to the nearest 0.1 kg on a beam balance scale. BMI was calculated as weight in kilograms divided by height in meters squared. The fasting blood specimen was separated by centrifugation, and the serum was frozen at -70°C and shipped to The University of Texas-Houston Health Science Center. Sera were analyzed for insulin, glucose, total cholesterol, triglycerides, and HDL cholesterol. Serum cholesterol, HDL cholesterol, and triglycerides were determined with standard protocols and dextran sulfate/Mg²⁺ precipitation.³⁶ Serum insulin levels were measured by standard radioimmunoassay techniques by use of a commercially available kit from Diagnostics Systems Laboratories. Serum glucose was determined with a Dupont Dimension AR by use of the hexokinase methodology. LDL cholesterol values were calculated by the Friedewald et al³⁷ equation. Ethnicity was classified according to that reported by the parent. All protocols and consent forms were approved by the University of Texas Houston Committee for the Protection of Human Subjects.

Statistical Analysis
Statistical analysis consisted of comparisons of median values of individual variables between ethnic groups for boys and girls by use of the nonparametric Mann-Whitney test. Similar comparisons were carried out by use of parametric methods. For analytic purposes, an adverse risk factor was defined to be present when a child's value for a particular variable exceeded the median value for the total study population, except for HDL cholesterol, for which values below the median were designated as conferring risk. The total group median values were chosen as the criteria for defining the absence or presence of a risk factor because accepted threshold values for abnormality have not been defined for all of these variables in children. Furthermore, the choice of the median provides greater power for studying clustering than would the choice of a more extreme cutoff point, such as the 75th (or 25th) percentile or 2 SD above (or below) the mean. Spearman correlations were used to determine the associations among the insulin resistance factors (insulin, triglycerides, systolic blood pressure, HDL cholesterol, and BMI). Only one blood pressure variable was examined for analytic purposes because of the expected strong correlations between blood pressure variables. Systolic blood pressure was chosen because it is likely to be measured more accurately and reproducibly than either diastolic variable in children.

Although this study did not measure insulin resistance directly, we explored the clustering of these factors to determine any ethnic differences in the degree of insulin resistance syndrome. PCA and summed Z scores were used in developing two summary measures characterizing the insulin resistance syndrome to compare measures of this syndrome across subgroups in the population. One summary score was created by converting each child's value of insulin, triglycerides, systolic blood pressure, HDL cholesterol, and BMI to Z scores and summing them for each individual. (The negative of the Z score was used for HDL cholesterol.) PCA, a multivariate analysis technique, was used to derive the other summary score. Because we were interested in characterizing risk factor clustering and the differences in the mean value of the risk factor cluster between sex-ethnic groups, other multivariate regression methods that are used primarily to relate risk factors to group membership or outcome, such as discriminate analysis or multiple logistic regression, were not appropriate for our purposes. PCA provides a method for exploring the random variation in several variables simultaneously and linearly combining a multidimensional set of variables into one dimension.^38,39 Algebraically, the first principal component, y₁, is a linear combination of x₁... x_p (ie, y₁=a₁₁x₁+a₁₂x₂+... a_1px_p), where a_p is the weights that are mathematically determined to maximize the sum of the squared correlations of the principal component with the original variables.^38,39 Variables of risk factors used in the principal components model were selected a priori. Variables with a skewed distribution-insulin, triglycerides, HDL cholesterol, and BMI-were log transformed to improve closeness to normality. Principal component models were run first for each sex-ethnic group separately to establish similarity of loading in all four groups. Then a single model was run for the entire study population. The first principal component, which was also the largest component for each sex-ethnic group, was used to develop a single index score representing the insulin resistance syndrome. Both the summed Z scores and the first principal component scores were then compared between Mexican-American and non-Hispanic white boys and girls by use of ANOVA. Data analyses were performed with the Stata statistical package.⁴⁰

	Results

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Median values and ranges for the variables of interest are given in Table 1 for each sex-ethnic group. Because the distributions of insulin, triglycerides, HDL cholesterol, and BMI were skewed, nonparametric methods were used to compare differences. Median levels of insulin and glucose were significantly higher in Mexican-American boys and girls than in non-Hispanic white boys and girls. Levels of HDL cholesterol were significantly lower in Mexican-American boys than in non-Hispanic white boys, whereas among girls these levels were similar among Mexican Americans and non-Hispanic whites. Similarly, systolic blood pressure and BMI were significantly higher in Mexican-American boys compared with non-Hispanic white boys and similar in the two groups of girls. Levels of total cholesterol, LDL cholesterol, triglycerides, and diastolic blood pressure were similar among all groups of children.

View this table: [in this window] [in a new window]   Table 1. Median and Range Values for Selected Characteristics Among Third-Grade Mexican-American and Non-Hispanic White Boys and Girls: The Corpus Christi Child Heart Study, 1994

Spearman correlations of factors associated with the insulin resistance syndrome stratified by sex and ethnicity are shown in Table 2. In general, the correlations were of moderate strength and consistent with the expected associations. The patterns of association were similar for Mexican Americans, both boys and girls, and for non-Hispanic white girls but not for non-Hispanic white boys, among whom the correlations were generally weaker.

View this table: [in this window] [in a new window]   Table 2. Spearman Correlations Among Risk Factors Associated With the Insulin Resistance Syndrome Among Third-Grade Mexican-American and Non-Hispanic White Boys and Girls: The Corpus Christi Child Heart Study, 1994

Fifty-five percent of Mexican-American children had three or more risk factors with levels above the median compared with only 37% of non-Hispanic white children. Three times as many Mexican-American as non-Hispanic white children had five adverse risk factors (15.8% versus 5.2%). The distributions of number of adverse risk factors by ethnicity and sex are shown in Fig 2. Similar proportions of Mexican-American and non-Hispanic white girls had three or more risk factors (52% versus 48%). However, twice as many Mexican-American girls had five adverse risk factors than non-Hispanic white girls (18% versus 9%). Mexican-American boys appeared to have a more adverse risk profile than non-Hispanic white boys. Fifty-nine percent of Mexican-American boys had three or more risk factors and 14% had five risk factors compared with 25% and 1%, respectively, of non-Hispanic white boys.

View larger version (26K): [in this window] [in a new window]   Figure 2. Distributions of risk factors among third-grade Mexican-American (MA) and non-Hispanic white (NHW) boys and girls: the Corpus Christi Child Heart Study, 1994. Risk factors are defined as values exceeding the median, except for HDL cholesterol, which is below the median.

PCA was used to create a summary score or index representing the insulin resistance syndrome and consisted of measures of fasting plasma insulin, triglycerides, systolic blood pressure, HDL cholesterol, and BMI. Four separate PCAs were performed to determine whether the factors loaded similarly for each sex-ethnic group. As shown in Table 3, the principal component coefficients were generally similar among the sex-ethnic groups. However, non-Hispanic white boys had HDL cholesterol loadings that were greater than in the other groups. Component 1 for all sex-ethnic groups included positive contributions from insulin, triglycerides, systolic blood pressure, and BMI and a negative contribution from HDL cholesterol. Thus, this component appeared to reflect insulin resistance. Because the loadings were similar, a component score reflecting insulin resistance was derived by use of the first component from a single principal components model for the total population.

View this table: [in this window] [in a new window]   Table 3. First Principal Component of Risk Factors Associated With the Insulin Resistance Syndrome Among Third-Grade Mexican-American and Non-Hispanic White Boys and Girls: The Corpus Christi Child Heart Study, 1994

Mean values for the sum of Z scores and for component 1 from the PCA are shown and compared by sex and ethnicity in Table 4. Mexican-American boys and girls had significantly higher mean values for both summary scores representing insulin resistance than non-Hispanic white boys and girls.

View this table: [in this window] [in a new window]   Table 4. Mean Values for Scores Representing the Insulin Resistance Syndrome Among Third-Grade Mexican-American and Non-Hispanic White Boys and Girls: The Corpus Christi Child Heart Study, 1994

	Discussion

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To test the hypothesis that the prevalence of the insulin resistance syndrome is greater among Mexican-American children compared with non-Hispanic white children, we used two approaches to integrate the cluster of interrelated risk factors that characterize the insulin resistance syndrome into a summary score. Using the sum of Z scores and PCA, we found that Mexican-American boys and girls had significantly higher mean values of the insulin resistance summary score than non-Hispanic white boys and girls. These results were supported by the finding of greater median levels of fasting plasma insulin, triglycerides, systolic blood pressure levels, lower HDL cholesterol levels, and a greater prevalence of multiple adverse risk factors in Mexican-American children compared with non-Hispanic white children. This apparent ethnic difference in insulin resistance was greater among boys than among girls, perhaps because of differences in adiposity. Compared with Mexican-American and non-Hispanic white girls who had similar BMIs, Mexican-American boys had a significantly higher median BMI than non-Hispanic white boys. The pattern and magnitude of Spearman correlations of risk factors were similar among Mexican-American girls and boys and non-Hispanic white girls, whereas non-Hispanic white boys demonstrated weaker correlations, perhaps also related to lesser adiposity. From these findings, we conclude that some of the factors responsible for the increased risk of NIDDM and CHD seen among Mexican-American adults are demonstrable in childhood. Whether this reflects genetic differences or early environmental influences remains to be determined.

We are aware of only one published study investigating insulin resistance in Mexican-American children. Stuart et al³⁵ reported a strong positive correlation between the severity of acanthosis nigricans and fasting insulin concentrations among an unselected population of Mexican- and African-American children. The present study is the first study to investigate and compare the distributions of the cluster of risk factors associated with insulin resistance between Mexican-American and non-Hispanic white children. Previous studies have shown higher fasting insulin levels and levels of other risk factors associated with insulin resistance to be higher among Mexican-American adults than among non-Hispanic white adults.⁶ In addition, Haffner et al³² demonstrated greater insulin resistance among young, lean Mexican-American adults compared with similar non-Hispanic white adults.

Several studies in children, adolescents, and young adults, including the present study, have shown that insulin levels are positively associated with levels of serum triglycerides, blood pressure, and BMI and negatively associated with HDL cholesterol.^41–45 In addition, Ronnemaa et al⁴³ and Bao et al⁴⁶ reported that the cluster of risk factors that characterize insulin resistance develops within the same individual among children, adolescents, and young adults and is shown to track over time. Among 1176 children 5 to 17 years of age enrolled in the Bogalusa Heart Study, 61% of the children who were in the highest quintile at baseline for adverse levels of systolic blood pressure, total cholesterol–to–HDL cholesterol ratio, and plasma insulin were also in the highest quintile 8 years later.⁴⁶ Similarly, 30% to 44% of Finnish children and adolescents who were in the highest fasting insulin quartile at baseline remained there 6 years later.⁴³ The documentation of the phenomenon of tracking adds strength to our inference that these differences, observed in children, are biologically meaningful.

There are several limitations to this study. First, the sample was not randomly assembled from the entire population of third-grade children in Corpus Christi. However, >90% of the children attend public school in Corpus Christi; thus, any selection bias introduced as a result of our sampling plan should be minimal. Second, participation fell short of recruitment goals; however, participation did not differ substantially between ethnic groups, and our participation rate of 53% is only slightly less than that of other school surveys, ie, 59% to 64%.⁴⁷ Although this remains a potential source of selection bias, the findings of this study compared with those from other studies suggest the relationships are real. For example, results from this study and others have reported greater BMI among elementary Hispanic children than among non-Hispanic whites.^47–49 Third, the insulin assay did not distinguish insulin from proinsulin. However, the contribution of proinsulin to measured insulin is minimal in a nondiabetic population^3,50; in this study, therefore, the lack of this distinction does not create appreciable bias. Finally, insulin resistance was not measured directly because it was not feasible under the conditions of the study; however, these variables have been correlated with insulin resistance in other studies.^1,7,8,26 Additional studies to validate these measures of insulin resistance in childhood would be helpful.

Our internally consistent results contribute to the strength of our study. First, greater median levels of risk factors were found among Mexican-American children than among non-Hispanic white children, especially boys. This result is supported by a greater prevalence of risk factors and greater magnitude of Spearman correlation coefficients among Mexican-American than non-Hispanic white boys and girls. Second, the pattern of coefficients for the first principal component was consistent among the groups of children. Finally, the mean summary score measures for the Mexican-American boys and girls were significantly greater than for non-Hispanic white boys and girls for both the sum of the Z score and PCA methods.

PCA was used to create a summary score to represent insulin resistance.^38,39 We are aware of no other study that has used this analytic technique to describe insulin resistance as a single index measure. Our model explained 44% of the variance in the five variables, with the remaining variance caused by genetic and environmental factors, intraindividual variability, and measurement error. Edwards et al⁵¹ used factor analysis to investigate 10 interrelated variables characterizing the insulin resistance syndrome using data from a large sample of nondiabetic women. Factor analysis reduced 10 variables to three factors that explained 66% of the variance in the data. The investigators concluded that each of the three factors may describe a different aspect of the insulin resistance syndrome.

Our results are consistent with the presence of the insulin resistance syndrome in childhood and support the hypothesis that Mexican-American children exhibit a greater degree of insulin resistance syndrome than non-Hispanic white children, especially among boys. The greater degree of insulin resistance syndrome among Mexican-American children compared with non-Hispanic white children may underlie the greater risk of NIDDM and/or CHD among Mexican-American adults. Insulin resistance plays an important role in the development of NIDDM, dyslipidemia, and hypertension, all of which contribute to atherosclerosis. The evidence from the present study that insulin resistance is already present in childhood provides the basis for considering the development of programs to detect and prevent these metabolic abnormalities in children. Further research is needed to show the degree to which insulin resistance in childhood is related to insulin resistance and NIDDM in early adulthood, especially among Mexican Americans.

	Selected Abbreviations and Acronyms

 

BMI = body mass index CHD = coronary heart disease NIDDM = non–insulin-dependent diabetes mellitus PCA = principal component analysis

	Acknowledgments

 
This investigation was supported by Public Health Service grant No. U48/CCU609653 awarded by the Centers for Disease Control and Prevention to the Southwest Center for Prevention Research.

	Footnotes

 
Guest editor for this article was Welton Gersony, MD, Babies Hospital, New York, NY.

Received August 13, 1996; revision received June 26, 1997; accepted September 7, 1997.

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