Published online October 2, 2006
PEDIATRICS Vol. 118 No. 5 November 2006, pp. e1516-e1522 (doi:10.1542/peds.2006-0845)
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rodríguez-Morán, M.
Right arrow Articles by Guerrero-Romero, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rodríguez-Morán, M.
Right arrow Articles by Guerrero-Romero, F.
Related Collections
Right arrow Endocrinology

ARTICLE

Hyperinsulinemia in Healthy Children and Adolescents With a Positive Family History for Type 2 Diabetes

Martha Rodríguez-Morán, MD, MSc, PhDa and Fernando Guerrero-Romero, MD, PhD, FACPb

a Medical Research Unit in Clinical Epidemiology of the Mexican Social Security Institute, Durango, Mexico
b Research Group on Diabetes and Chronic Illnesses, Durango, Mexico


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
OBJECTIVE. Our goal was to determine the relationship between family history of type 2 diabetes and fasting hyperinsulinemia in healthy children and adolescents.

METHODS. A total of 317 children and adolescents, 10 to 14 years of age with Tanner stage 1 or 2, were randomly selected from elementary and middle schools in Durango, northern Mexico, to participate in a cross-sectional, community-based study. Family history was ascertained by a direct, detailed medical examination that included anthropometric and laboratory measurements from both parents. We determined the prevalence of family history of type 2 diabetes, high blood pressure, obesity, hyperinsulinemia, and the adjusted odds ratio that computes the relationship between hyperinsulinemia and family history of type 2 diabetes.

RESULTS. Family history of type 2 diabetes, high blood pressure, and obesity was recognized in 30 (9.2%), 61 (18.7%), and 74 (22.7%) children and adolescents, respectively. Children and adolescents with positive family history showed higher systolic and diastolic blood pressure, were more obese, and exhibited significantly higher fasting insulin and triglycerides levels, as well as a higher homeostasis model analysis insulin resistance index, than children with negative family history. A total of 48 (15.1%) children and adolescents exhibited hyperinsulinemia, 35 (72.9%) with and 13 (27.1%) without family history. The odds ratio adjusted by gender, fat mass (kilograms and percent), waist circumference, BMI, and Tanner stage showed that family history of diabetes, but not high blood pressure and obesity, was independently related with hyperinsulinemia.

CONCLUSIONS. Among children and adolescents, family history of diabetes, but not high blood pressure and obesity, is independently associated with hyperinsulinemia.

Key Words: epidemiology • diabetes mellitus • family issues • obesity

Abbreviations: FH-D—family history of type 2 diabetes • HBP—high blood pressure • FH-HBP—family history of high blood pressure • FH-O—family history of obesity • HDL-C—high-density lipoprotein cholesterol • LDL-C—low-density lipoprotein cholesterol • HOMA-IR—homeostasis model analysis insulin resistance • CI—confidence interval • IGT—impaired glucose tolerance • OR—odds ratio

A growing body of evidence on the increase of obesity among youth1–4 shows that obese children and adolescents exhibit a clustering of risk factors for coronary heart disease5,6 and metabolic glucose disturbances.7,8 Insulin levels positively correlate with obesity, particularly with abdominal obesity or visceral fat9,10 and indices of insulin secretion and insulin action,11 such that hyperinsulinemia may help in evaluation for the risk for diabetes and cardiovascular disease in children.11,12

Interestingly, several studies in adults have shown that family history of type 2 diabetes (FH-D) is associated with hyperinsulinemia irrespective of obesity.13–15 Not all obese individuals show insulin resistance,16 and some nonobese subjects have decreased insulin sensitivity.17 These findings suggest that in addition to obesity, other factors, such as FH-D, could play an important role in the development of insulin resistance.18 However, studies reporting that family history is an important surrogate measure for estimating metabolic or cardiovascular risk in offspring have collected data about parental history by questionnaire, asking whether either or both parents had history of heart attack, diabetes, high blood pressure (HBP), or stroke,18–21 possibly introducing a significant source of bias.

In this study, we obtained data on parental history by direct, detailed medical examination and laboratory measurements from both parents and tested the hypothesis that FH-D is independently associated with fasting hyperinsulinemia in healthy children and adolescents.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
With the approval of protocol by the Mexican Social Security Institute Research Committee, and after obtaining the informed consent from children and their parents, a cross-sectional, population-based study was conducted. The study population was determined according to 2-stage cluster sampling. In the first stage, a random sample of elementary and middle schools in Durango, northern Mexico, were obtained; in the second stage, children aged 10 to 14 years, randomly selected from these schools, were invited to participate.

All participants were required to be in good health. For this purpose, before their inclusion at study, both detailed medical history and complete physical examination were performed. Children and adolescents with diagnosis of acute or chronic illnesses, infections, renal or hepatic diseases, pr neoplasia or under medical treatment were not included. Tanner stage was determined22 by 1 pediatrician of the Medical Research Unit; only children at Tanner stage 1 or 2 were included.

Family history of high blood pressure (FH-HBP) and FH-D were ascertained by (a) direct detailed medical examination and laboratory measurements from both parents, and (b) verification of clinical records. Laboratory measurements included fasting glucose levels and an oral-glucose tolerance tests for parents with and without previous diagnosis of diabetes, according to the criterion of the American Diabetes Association.23 Blood pressure measurement technique and criterion for diagnosing hypertension using a mercury sphygmomanometer followed the recommended procedures from the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure24; parents with previous diagnosis of hypertension taking antihypertensive drugs were considered hypertensive irrespective of their systolic and diastolic blood pressure. Family history of obesity (FH-O) was ascertained by direct measurements of weight, waist circumference, body fat mass, and percent body fat from both parents. Obesity in parents was defined as BMI ≥30 kg/m2.

Measurements
Weight and height were measured between 8:00 AM and 9:00 AM, with children in standing position, wearing light clothing, and without shoes. BMI was calculated as weight (in kilograms) divided by height (in meters) squared. Waist circumference was measured to the nearest centimeter with a flexible steel tape measure. The following anatomic landmarks were used: laterally, midway between the lowest portion of the rib cage and iliac crest, and anteriorly midway between the xiphoid process of the sternum and the umbilicus.25 All measurements were taken by pediatricians from the Medical Research Unit. The intra- and interassay variation coefficients were 1.1 and 1.7%, respectively.

Blood pressure measurements were taken using a mercury sphygmomanometer, with the children seated and their arms bared and supported at heart level, after at least 5 minutes of rest, and using an appropriate cuff size.24 An average of 3 readings separated by 2 minutes was used.

Assays
A venous whole blood sample was collected after 8 to 10 hours of fasting and 2-hour postload glucose (1.75 mg of glucose per kilogram of body weight). Total cholesterol and triglycerides were enzymatically measured (Data Pro Plus random access clinical analyzer, Waltham, MA). The high-density lipoprotein cholesterol (HDL-C) fraction was obtained after precipitation by phosphotungstic reagent. The intra- and interassay coefficients of variation were 1.7% and 2.8% for total cholesterol, 1.7% and 3.1% for triglycerides, and 1.3% and 2.6% for HDL-C. Low-density lipoprotein cholesterol (LDL-C) was calculated using the Friedewald formula. Serum glucose was measured using the glucose-oxidase method; the intraassay and interassay coefficients of variation were 1.1% and 1.5%, respectively. Insulin levels were measured by microparticle enzyme immunoassay (Abbot Axsym System, Bedford, MA), with intra- and interassay variation coefficients of 4.5 and 6.9, respectively.

Definitions
Obesity was defined by BMI ≥95th percentile, overweight by BMI between the 85th and 95th percentiles, and normal weight by BMI <85th percentile. BMI cutoff values used were age- and gender-specific according to the childhood international BMI cutoff charts.26 High blood pressure (HBP) was defined as systolic and diastolic blood pressure ≥95th percentile for age and gender.

The cutoff values for abnormal serum lipid levels were based on the National Cholesterol Education Program Pediatric Panel Report.27 Hypertriglyceridemia, hypercholesterolemia, low HDL-C, and high LDL-C were defined by serum concentrations of triglycerides ≥150 mg/dL, total cholesterol ≥170 mg/dL, HDL-C ≤35 mg/dL, and LDL-C ≥110 mg/dL.

Hyperinsulinemia was defined on the basis of fasting serum insulin levels ≥85th percentile, which was previously determined in an independent cohort of 748 children and adolescents from our community. The cutoff value for hyperinsulinemia corresponds to 16 µIU/mL for this stratum of age (M.R.-M. and F.G.-R., unpublished data, 2005). The cutoff value for normal fasting glucose was 100 mg/dL.

The homeostasis model analysis insulin resistance (HOMA-IR = fasting glucose mmol/L x fasting insulin µIU/mL/22.5) index was used for estimating insulin action.28

Statistical Analysis
Numerical values are reported as mean ± SD. For bivariate analysis, the unpaired Student's t test (Mann-Whitney U test) or {chi}2 test was used. P value for trend was used for estimating differences between multiple groups. Correlation analysis was performed using the Pearson test (Spearman test).

Multivariate logistic regression adjusted by gender, fat mass, waist circumference, age, and Tanner stage was used to compute the relationship between FH-D, FH-HBP, and FH-O (independent variables) and the presence of hyperinsulinemia (dependent variable). A 95% confidence interval (CI) was considered. Data were analyzed by using SPSS 12.0 for Windows (SPSS Inc, Chicago, IL).


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
A total of 317 children (157 [49.5%] girls and 160 [50.5%] boys, with an average age (±SD) of 12.0 ± 1.5 years, were enrolled. Positive family history was identified in 119 (37.5%) children (55 [46.2%] girls and 64 [53.8%] boys) (P = .425).

Girls were significantly younger than boys (11.6 ± 1.4 vs 12.1 ± 1.5 years; P = .009), whereas other variables such as weight (50.1 ± 15.8 vs 49.5 ± 13.2 kg; P = .721), waist circumference (74.4 ± 14.1 vs 71.9 ± 11.8 cm; P = .793), and BMI (21.1 ± 4.9 vs 21.3 ± 4.3 kg/m2; P = .09) did not show significant statistical differences between girls and boys.

Anthropometric and laboratory characteristics of parents are shown in Table 1. As was expected, because children's parents with positive family history had diabetes, hypertension, and/or obesity, they showed higher glucose levels and blood pressure, and were more obese than children's parents in the control group. There was a significant positive correlation between the BMI of the parents and their offspring (r = 0.255, P < .001 and r = 0.196, P < .05, for the groups with and without family history, respectively), but none between other anthropometric and biochemical measurements.


View this table:
[in this window]
[in a new window]

  		TABLE 1 Anthropometric and Laboratory Characteristics of Children's Parents

 
FH-D, FH-HBP, and FH-O were recognized in 30 (9.2%), 61 (18.7%), and 74 (22.7%) children and adolescents, respectively. Table 2 shows the characteristics of the targeted population. Children and adolescents with positive family history showed higher systolic and diastolic blood pressure, were more obese, and exhibited significant higher fasting insulin and triglyceride levels, as well as higher HOMA-IR index, than children with negative family history.


View this table:
[in this window]
[in a new window]

  		TABLE 2 Anthropometric and Laboratory Characteristics of Children and Adolescents According to the Presence of Family History (N = 317)

 
A total of 48 (15.1%) children and adolescents exhibited hyperinsulinemia, 35 (72.9%) and 13 (27.1%) with and without family history, respectively. Among children and adolescents with hyperinsulinemia, there were not significant statistical differences between girls (n = 25) and boys (n = 23) for age (11.9 ± 1.4 vs 11.6 ± 1.3 years; P = .337), weight (66.1 ± 24.1 vs 57.0 ± 1.4 kg; P = .181), waist circumference (90.1 ± 20.0 vs 80.9 ± 8.4 cm; P = .119), or BMI (26.6 ± 6.2 vs 24.5 ± 3.4 kg/m2; P = .296).

Stratified by BMI, hyperinsulinemia was identified in 6 (3.2%) normal-weight, 7 (12.1%) overweight, and 35 (47.9%) obese children and adolescents; among them, all the normal-weight and overweight but only 22 (62.8%) obese children had positive family history. Moreover, irrespective of obesity, hyperinsulinemic children showed higher blood pressure, unfavorable lipid profiles, and higher glucose levels (Table 3).


View this table:
[in this window]
[in a new window]

  		TABLE 3 Anthropometric and Laboratory Characteristics of Children According to BMI and Hyperinsulinemia

 
Table 4 shows the characteristics of children and adolescents according to family history and hyperinsulinemia. In both groups, children with hyperinsulinemia exhibited the highest obesity indices, HOMA-IR index, and triglyceride levels. Furthermore, without significant statistical differences, fasting and 2-hour postload glucose levels also were higher among children with positive family history.


View this table:
[in this window]
[in a new window]

  		TABLE 4 Anthropometric and Laboratory Characteristics of the Children With Positive and Negative Family History and Hyperinsulinemia

 
Impaired glucose tolerance (IGT) was identified in 49 (15.4%) children, 27 (22.7%) in the group with positive family history and 22 (11.1%) in the group without it. All children with negative family history and IGT were obese, whereas among children with positive family history and IGT, 11 (40.7%) had normal weight. There were not children with diabetes in the sample.

Forty-five (14.2%) children and adolescents exhibited dyslipidemia, 32 (26.9%) and 13 (6.6%) in the groups with and without family history. Among children with dyslipidemia and positive family history, 56.3% (18/32) were not obese. Twenty-seven (55.1%) of 49 children with IGT exhibited dyslipidemia; among them, 22 (44.9%) of 49 in the group had positive family history.

Fasting serum insulin levels correlated with FH-D (r = 0.336; P < .05), fat mass (r = 0.572; P < .001), and waist circumference (r = 0.553; P < .001).

The odds ratio (OR), adjusted by fat mass, waist circumference, BMI, gender, and Tanner stage, that computes the relationship between family history and hyperinsulinemia are shown in Table 5. FH-D, but not FH-HBP or FH-O, was independently associated with elevated fasting insulin levels.


View this table:
[in this window]
[in a new window]

  		TABLE 5 Estimated OR (95% CI) Between Family Phenotype (Independent Variables) and Hyperinsulinemia (Dependent Variable) Among Children and Adolescents Aged 10 to 14 Years (n = 317)

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
Previously, it has been described that obese offspring of subjects with type 2 diabetes have hyperinsulinemia, suggesting that FH-D is a risk factor for insulin resistance.18,29,30 However, to the best of our knowledge, our study is the first to obtain data on family history by direct measurements and detailed medical history from both parents of the offspring. Our data show that the FH-D is independently associated with hyperinsulinemia and that it can be found even among the normal-weight offspring of subjects with diabetes. Moreover, this study shows that children and adolescents with hyperinsulinemia, irrespective of obesity, exhibited an unfavorable lipid profile and upper percentiles of blood pressure, suggesting that young people with hyperinsulinemia also may have a cluster of risk factors for the future development of cardiovascular disease.

In addition, the present study also demonstrates that youth with FH-D have significantly higher insulin resistance than children who do not have family history; this finding agrees with previous reports that showed that FH-D is independently and negatively associated to insulin sensitivity.31,32 Both hyperinsulinemia and insulin resistance contribute to development of type 2 diabetes, but discussion about which is the earliest metabolic alteration associated with the FH-D currently is in progress. Whether hyperinsulinemia is an early compensation for decreased insulin sensitivity or it is a primary defect in the offspring of subjects with type 2 diabetes needs to be adequately addressed.

Because obesity in childhood has significantly increased in recent years2–4,33 and it is strongly associated with insulin resistance,32 the main public health policies are focused on screening obese children and adolescents. However, our data show that hyperinsulinemia and its related adverse lipid profile also are strongly associated with FH-D and can be found among normal-weight children, supporting the statement that screening for cardiovascular and metabolic risk factors in childhood should not be restricted solely to obese children.34 Taking into account that FH-D is associated with earliest metabolic alterations, we postulate that FH-D also should be a criterion for screening apparently healthy, young populations.34

Moreover, our results show that normal-weight, overweight, and obese children and adolescents with hyperinsulinemia exhibited similar metabolic abnormalities and higher blood pressure values, supporting the finding that, in addition to obesity, other critical factors are related to development of hyperinsulinemia and dyslipidemia in childhood. Our results agree with the report by Cruz et al,17 which showed that fat mass is not related to features of metabolic syndrome.

Forty-nine children (15.4%) were found to have IGT. Previous studies in obese children reported a prevalence of IGT that varies from 4.5% to 28%.8,35,36 In children and adolescents with marked obesity, the prevalence of IGT raises 21%,36 whereas in overweight Latino children with FH-D it raises 28%.8 In our study, overall prevalence of IGT was significantly lower than that reported by Sinha et al,36 differences that could be explained by different age and adiposity of the targeted population. However, among children and adolescents with FH-D, prevalence of IGT in our study population was similar (22.7% vs 28%) to that reported by Goran et al.8 Moreover, similar to reports by Goran et al,8 our data show that IGT in the offspring of subjects with type 2 diabetes is not related to obesity, whereas among children and adolescents who do not have FH-D, prevalence of IGT is closely related to the presence of obesity.

Several limitations of this study deserve to be mentioned. First, coinheritance of insulin resistance and its comorbidities are age dependent; thus, taking into account the average age of parents (38.3 ± 5.6 years) in this study, it is likely that some of them, currently healthy, will get diabetes, obesity, or HBP in the future. This confounding variable may exert a potential source of bias, but because it is not possible to control this limitation in cross-sectional design studies, follow-up research will be required. Second, we did not measure the customary diet. Thus, we are not certain about the role of caloric and lipid ingestion on the risk for development of hyperinsulinemia and dyslipidemia. Interestingly, obesity in the parents was strongly correlated with obesity in the offspring, which could reflect inheritable susceptibility and/or environmental influences related with parental feeding practices. However, taking into account that even some normal-weight children and adolescents exhibited an unfavorable lipid profile and high serum insulin levels, this limitation exerts a slight influence on our conclusions.

Finally, to minimize the well-known pubertal effect on insulin levels and the adiposity rebound, a marker for generalized growth acceleration and fat hyperplasia that may be a critical period in childhood for development of obesity,37 only children and adolescents with Tanner stage 1 or 2, and 10 to 14 years of age, were included.


   CONCLUSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
Our data show that in healthy children and adolescents, FH-D but not FH-HBP or FH-O is independently associated with hyperinsulinemia, emphasizing the importance of parental history of diabetes for the implementation of screening strategies.


   ACKNOWLEDGMENTS
 
This work was supported by grants from the Combined Fund CONACYT-State of Durango Government (FOMIX Dgo-2002-C01-3762), the Research Promotion Fund of the MSSI (FP 2003/160), and the Mexican Social Security Institute Foundation, AC.


   FOOTNOTES
 
Accepted May 26, 2006.

Address correspondence to Fernando Guerrero-Romero, MD, PhD, FACP, Siqueiros 225 esq./Castañeda, 34000 Durango, Durango, Mexico. E-mail: guerrero_romero{at}hotmail.com

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

  1. Troiano RP, Flegal KM, Kuczmarski RJ, Campbell SM, Johnson CL. Overweight prevalence in trends for children and adolescents: the National Health and Nutrition Examination Surveys, 1963–1991. Arch Pediatr Adolesc Med. 1995;149 :1085 –1091[Abstract]
  2. del Rio-Navarro BE, Velázquez-Monroy O, Sánchez-Castillo CP, et al. The high prevalence of overweight and obesity in Mexican children. Obes Res. 2004;12 :215 –223[ISI][Medline]
  3. Daniels SR, Arnett DK, Eckel RH, et al. Overweight in children and adolescents: pathoiphysiology, consequences, prevention, and treatment. Circulation. 2005;111 :1999 –2012[Abstract/Free Full Text]
  4. Slyper AH. The pediatric obesity epidemic: causes and controversies. J Clin Endocrinol Metab. 2004;89 :2540 –2547[Abstract/Free Full Text]
  5. Raitakari OT, Porkka KV, Rönnema T, Akerblom HK. Clustering of risk factors for coronary heart disease in children and adolescents: the Cardiovascular Risk in Young Finns Study. Acta Paediatr. 1994;83 :935 –940[ISI][Medline]
  6. Freedman DA, Dietz WH, Srinivasan SR, Berenson GS. The relation of cardiovascular of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics. 1999;103 :1175 –1182[Abstract/Free Full Text]
  7. Dietz WH. Overweight and precursors of type 2 diabetes mellitus in children and adolescents. J Pediatr. 2001;138 :453 –454[CrossRef][ISI][Medline]
  8. Goran MI, Bergman RN, Avila Q, et al. Impaired glucose tolerance and reduced ß-cell function in overweight Latino children with a positive family history for type 2 diabetes. J Clin Endocrinol Metab. 2004;89 :207 –212[Abstract/Free Full Text]
  9. Wilson DM, Wang Y, Cullen KW, et al. Assessing weight-related biochemical cardiovascular risk factors in African-American girls. Obes Res. 2004;12 :73S –83S[ISI][Medline]
  10. Raitakari OT, Porkka KV, Ronnemaa T, et al. The role of insulin in clustering of serum lipids and blood pressure in children and adolescents. The Cardiovascular Risk in Young Finns study. Diabetologia. 1995;38 :1042 –1050[ISI][Medline]
  11. Cruz ML, Bergman RN, Goran MI. Unique effect of visceral fat on insulin sensitivity in obese Hispanic children with a family history of type 2 diabetes. Diabetes Care. 2002;25 :1631 –1636[Abstract/Free Full Text]
  12. Fujimoto WY, Leonetti DL, Newell-Moris L, Shuman WP, Wahl PW. Relationship of absence or presence of a family history of diabetes to body weight and body fat distribution in type 2 diabetes. Int J Obes (Lond). 1991;15 :111 –120
  13. Rodríguez-Morán M, Guerrero-Romero F. The parental phenotype of diabetes, but not of essential hypertension, is linked to the development of metabolic syndrome in Mexican individuals. Acta Diabetologica. 2001;38 :87 –91[CrossRef][ISI][Medline]
  14. Guerrero-Romero F, Rodríguez-Morán M, González-Ortiz M, Martínez-Abundis E. Insulin action and secretion in healthy Hispanic-Mexican first-degree relatives of subjects with type 2 diabetes. J Endocrinol Invest. 2001;24 :580 –586[ISI][Medline]
  15. Ferrannini E, Natali A, Bell P, Cavallo-Perai P, Lalic N, Miagrone G. Insulin resistance and hypersecretion in obesity. J Clin Invest. 1997;100 :1166 –1173[ISI][Medline]
  16. Hollenbeck C, Reaven GM. Variations in insulin-stimulated glucose uptake in healthy individuals with normal glucose tolerance. J Clin Endocrinol Metab. 1987;64 :1169 –1173[Abstract]
  17. Cruz ML, Weigensberg MJ, Huang T-K, Ball G, Shaibi GQ, Goran MI. The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity. J Clin Endocrinol Metab. 2004;89 :108 –113[Abstract/Free Full Text]
  18. Haffner SM, Stern MP, Miettinen H, Gingerich R, Bowsher RR. Higher proinsulin and specific insulin are both associated with parental history of diabetes. Diabetes. 1995;44 :1156 –1160[Abstract]
  19. Bao W, Srinivasan SR, Wattigney WA, Berenson GS. The relation of parental cardiovascular disease to risk factors in children and young adults: the Bogalusa Heart Study. Circulation. 1995;91 :365 –371[Abstract/Free Full Text]
  20. Chen W, Srinivasan SR, Elkasabany A, Berenson GS. Cardiovascular risk factors clustering features of insulin resistance syndrome (syndrome X) in a biracial (black-white) population of children, adolescents, and young adults: the Bogalusa Heart Study. Am J Epidemiol. 1999;150 :667 –674[Abstract/Free Full Text]
  21. Chen W, Srinivasan SR, Elkasabany A, Berenson GS. The association of cardiovascular risk factor clustering related to insulin resistance syndrome (Syndrome X) between young parents and their offspring: the Bogalusa Heart Study. Atherosclerosis. 1999;145 :197 –205[CrossRef][ISI][Medline]
  22. Tanner JM, Whitehouse RH, Takaishi M. Standards from birth to maturity for height, weight, height and weight velocity: British children, 1965. Arch Dis Child. 1996;41 :454 –495
  23. Expert Committee on the diagnosis and classification of diabetes mellitus. Position statements: diagnosis and classification of diabetes mellitus. Diabetes Care. 2004;27 :S5 –S10[CrossRef][Medline]
  24. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [published correction appears in Arch Intern Med. 1998;158:573]. Arch Intern Med. 1997;157 :2413 –2446[Abstract]
  25. Maffeis C, Pietrobelli A, Grezzani A, Provera S, Tatò L. Waist circumference and cardiovascular risk factors in prepubertal children. Obes Res. 2001;9 :179 –187[ISI][Medline]
  26. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ. 2000;320 :1240 –1245[Abstract/Free Full Text]
  27. National Cholesterol Education Panel. Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. NIH Publication 91–2732 Bethesda, MD: National Institutes of Health; 1991
  28. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28 :412 –419[CrossRef][ISI][Medline]
  29. Matsumoto K, Sakamaki H, Izumino K, et al. Increased insulin sensitivity and decreased insulin secretion in offspring of insulin-sensitive type 2 diabetic patients. Metabolism. 2000;49 :1219 –1223[CrossRef][ISI][Medline]
  30. Vaag A, Lehtovirta M, Thye-Ronn P, Groop L; European Group of Insulin Resistance. Metabolic impact of a family history of type 2 diabetes: results from a European multicentre study (EGIR). Diabet Med. 2001;18 :533 –540[CrossRef][ISI][Medline]
  31. Arslanian SA, Bacha F, Saad R, Gungor N. Family history of type 2 diabetes is associated with decreased insulin sensitivity and an impaired balance between insulin sensitivity and insulin secretion in white youth. Diabetes Care. 2005;28 :115 –119[Abstract/Free Full Text]
  32. Cisneros-Tapia R, Navarrete FA, Gallegos AC, Robles-Sardin AE, Méndez RO, Valencia ME. Insulin sensitivity and associated risk factors in Mexican children and adolescents. Diabetes Care. 2005;28 :2546 –2547[Free Full Text]
  33. Ebbeling CB, Pawlak DB, Ludwig DS. Chilhood obesity: public health crisis, common sense cure. Lancet. 2002;360 :473 –482[CrossRef][ISI][Medline]
  34. Rodríguez-Morán M, Salazar-Vázquez B, Violante R, Guerrero-Romero F. Metabolic Syndrome among children and adolescents aged 10 to 18 years. Diabetes Care. 2004;27 :2516 –2517[Free Full Text]
  35. Invitti C, Guzzaloni G, Gilardini L, Morabito F, Viberti G. Prevalence and concomitants of glucose intolerance in European obese children and adolescents. Diabetes Care. 2003;26 :118 –124[Abstract/Free Full Text]
  36. Sinha R, Fisch G, Teague B, et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med. 2002;346 :802 –810[Abstract/Free Full Text]
  37. Whitaker RC, Pepe MS, Wright JA, Seidel KD, Dietz WH. Early adiposity rebound and the risk of adult obesity. Pediatrics. 1998;101(3) . Available at:www.pediatrics.org/cgi/content/full/101/3/e5
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics



This article has been cited by other articles:


Home page
 Br Med BullHome page
K. A. Matyka
Type 2 diabetes in childhood: epidemiological and clinical aspects
Br. Med. Bull., June 1, 2008; 86(1): 59 - 75.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rodríguez-Morán, M.
Right arrow Articles by Guerrero-Romero, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rodríguez-Morán, M.
Right arrow Articles by Guerrero-Romero, F.
Related Collections
Right arrow Endocrinology