BACKGROUND: The severity of the metabolic syndrome (MetS) is related to future incidence of type 2 diabetes (T2DM) and cardiovascular disease (CVD). However, the relationship between MetS severity and levels of fasting insulin and adiponectin-markers of insulin resistance-is unclear.METHODS: We used linear and logistic regression to analyze data from 711 participants of the Princeton Lipid Research Cohort with information regarding levels of insulin, adiponectin and MetS severity during 1998-2003 (mean age 39.5 years); 595 participants had MetS severity data from childhood (1973-1976, mean age 12.9 years) and 417 had updated disease status from 2010 to 2014 (mean age 50.9 years).RESULTS: Childhood MetS Z-scores were positively associated with adult insulin levels (P < 0.001) and negatively associated with adiponectin levels (P = 0.01). In individual analyses, higher insulin levels and MetS Z-score as adults were related to higher odds of incident diabetes and CVD over the next 11.2 years (all P < 0.001), whereas lower adiponectin levels were only related to odds of future T2DM (P < 0.0001). In a model including insulin, adiponectin and MetS Z-score, adiponectin was not linked to future disease; both insulin (P = 0.027) and MetS Z- score (P = 0.002) were related to risk of future T2DM, while only MetS Z- score was related to future CVD (P < 0.001).CONCLUSIONS: The severity of MetS exhibits long-term links to levels of insulin and adiponectin, suggesting potential genetic and environmental influences on insulin resistance over time. As a long-term predictor of T2DM and CVD, the severity of MetS exhibited consistent independent correlations. This supports clinical utility in evaluating MetS severity as a predictor of risk for future disease.

Objectives: We evaluated associations involving a combination of healthy lifestyle factors and adults' long-term change in cardiometabolic disease (CMD) risk. Methods: We included 431 participants from the National Heart, Lung and Blood Institute Lipid Research Clinics (LRC) and Princeton Follow-up Studies (PFS). Results: Compared to those without healthy lifestyle practices, participants with one, 2, and >= 3 healthy lifestyle factors have 35%, 62% and 59% lower risk of CMD respectively. These health benefits were similar for both men and women. Conclusion: Combined healthy lifestyle factors were associated with a reduced likelihood of long-term CMD risk for both men and women. Maintaining or adopting healthy lifestyle behaviors, even later in life, may be beneficial for cardiometabolic health.

AIMS/HYPOTHESIS:The aim of this study was to determine the long-term associations of a sex- and race/ethnicity-specific metabolic syndrome (MetS) severity z score from childhood and adulthood with a future diagnosis of type 2 diabetes mellitus.METHODS:We performed a prospective cohort study with evaluations from the Cincinnati Clinic of the National Heart Lung and Blood Institute Lipids Research Clinic (LRC) 1973-1976 and Princeton Follow-up Study (PFS) 1998-2003, and further disease status from the Princeton Health Update (PHU) 2010-2014. We assessed MetS severity as a predictor of incident type 2 diabetes among 629 cohort participants assessed at both the LRC and PFS and 354 participants at the PHU.RESULTS:Cohort participants had a mean age of 12.9 years at baseline (LRC), 38.4 years at the PFS and 49.6 years at the most recent follow-up. Childhood MetS z scores were associated with adult MetS z scores (p < 0.01). Compared with individuals who were disease-free at all time-points, those who developed type 2 diabetes by 1998-2003 and 2010-2014 had higher MetS severity z scores in childhood (p < 0.05). For every one-unit elevation in childhood MetS z score, the OR of developing future type 2 diabetes was 2.7 for incident disease by a mean age of 38.5 years (p < 0.01) and 2.8 for incident disease by a mean age of 49.6 years (p < 0.05). Regarding associations with the change in z score from childhood to adulthood, for every one-unit increase in MetS z score over time the OR of developing incident type 2 diabetes by a mean age of 49.6 years was 7.3 (p < 0.01).CONCLUSIONS/INTERPRETATION:The severity of MetS in childhood was associated with the incidence of adult type 2 diabetes and the degree of increase in this severity predicted future disease. These findings provide evidence of potential clinical utility in assessing MetS severity to detect risk and follow clinical progress over time.

Objective. Assess whether adolescent oligomenorrhea (age 14-19) tracks into young adulthood (age 20-28) and predicts increased cardiometabolic risk factors, metabolic syndrome (MetS), and impaired fasting glucose-type II diabetes mellitus (IFG + T2DM).Materials and methods. Prospective study of menstrual cyclicity and its metabolic effects in 865 black and white schoolgirls from age 9 to 19, and 605 of these 865 girls from age 20 to 28.Main findings. Patterns of menstrual delays (oligomenorrhea) during ages 14-19 and ages 20-28 were closely related (p <.0001). Adolescent menses delay (ages 14-19, p <.0001), mean insulin (ages 20-28, p =.0003), and self-identified polycystic ovary syndrome (PCOS, p =.049) predicted ages 20-28 menses delay. Menses delays during ages 14-19 and 20-28, and, their interaction product were correlated with IFG + T2DM and MetS at ages 20-28. Waist circumference (ages 20-28, p <.0001), mean triglyceride (ages 20-28, p =.005), and the number of average menstrual cycles >= 42 days (ages 20-28, p =.04) predicted IFG + T2DM (ages 20-28). MetS (ages 9-19, p <.0001), mean insulin (ages 20-28, p =.0002), the number of 242 day gaps between menstrual periods (ages 20-28, p =.02), and cigarette smoking at age 18-19 (p =.04) were significant explanatory variables for MetS at ages 27-28. As MetS status category changed from age 14-19 to 27-28 from best to worst: (no -> no), (yes -> no), (yes -> yes), (no -> yes), the number of women with >= 2 menses delays during ages 20-28 rose from 3% to 4% to 15% to 17%, p =.0001. MetS status change from age 9-19 to 27-28 was positively associated with mean insulin (age 20-28, p <.0001), cigarette smoking (age 24-25, p =.01) and the number of menses delays during ages 20-28 (p =.04).Principal conclusions. Menstrual patterns track from adolescence to young adulthood, and oligomenorrhea predicts MetS and IFG + T2DM. Patterns of menses delays in adolescence should be considered as a significant risk factor for future development of young adult IFG + T2DM, MetS, oligomenorrhea, and polycystic ovary syndrome. (C) 2015 Elsevier Inc. All rights reserved.

OBJECTIVE:To assess adolescent and young adult determinants of visceral adipose tissue (VAT) at ages 26-28 years.STUDY DESIGN:Prospective study (ages 9-28 years) of cardiometabolic measures, menarche age, menses irregularities, metabolic syndrome, impaired fasting glucose-type 2 diabetes mellitus, and VAT in 400 girls (248 black, 152 white).RESULTS:Adolescent (age 14-19) independent variables for greater VAT at ages 26-28 included larger mean waist circumference (partial R(2) = 30.8%), earlier age at menarche (0.9%), and white race (1.8%). Young adult (ages 20-28 years) independent variables for greater VAT included larger mean waist circumference (partial R(2) = 61.7%), greater triglyceride levels (3.3%), lower high-density lipoprotein cholesterol (1.0%), and greater insulin resistance (homeostasis model assessment-estimated insulin resistance; 0.4%). Independent variables for greater VAT when both adolescent and young adult variables were used included waist (tertile rank change from adolescence to young adulthood, partial R(2) = 58.3%), greater young adult triglyceride levels (4.4%), white race (1.8%), greater young adult homeostasis model assessment-estimated insulin resistance (age 20-28, 2.4%), and earlier menarche age (0.7%). Menses irregularities were not independently associated with young adult VAT.CONCLUSIONS:Adolescent girls with early menarche and larger waist circumference should be targets for primary prevention of accretion of VAT. In young adulthood, VAT is associated with dysregulated cardiometabolic profiles, which is greater for those with waist circumference increases from adolescence to adulthood. Waist circumference during young adulthood, and to a lesser degree during adolescence, is an inexpensive surrogate for VAT at ages 26-28 years.

Dyslipidemia is a major risk factor for CVD. Previous studies on lipid heritability have largely focused on white populations assessed after the obesity epidemic. Given secular trends and racial differences in lipid levels, this study explored whether lipid heritability is consistent across time and between races. African American and white nuclear families had fasting lipids measured in the 1970s and 22–30 years later. Heritability was estimated, and bivariate analyses between visits were conducted by race using variance components analysis. A total of 1,454 individuals (age 14.1/40.6 for offspring/parents at baseline; 39.6/66.5 at follow-up) in 373 families (286 white, 87 African American) were included. Lipid trait heritabilities were typically stronger during the 1970s than the 2000s. At baseline, additive genetic variation for LDL was significantly lower in African Americans than whites (P = 0.015). Shared genetic contribution to lipid variability over time was significant in both whites (all P < 0.0001) and African Americans (P ≤ 0.05 for total, LDL, and HDL cholesterol). African American families demonstrated shared environmental contributions to lipid variation over time (all P ≤ 0.05). Lower heritability, lower LDL genetic variance, and durable environmental effects across the obesity epidemic in African American families suggest race-specific approaches are needed to clarify the genetic etiology of lipids.

Objective. We determined whether simple, clinical information on late and early menarche could help identify adult women with metabolic syndrome (MetS) and oligomenorrhea.Materials/Methods. We carried out a 26-year prospective follow-up of 272 suburban schoolgirls from ages 5-22 to 30-46.Results. Early menarche (<= 10 years, 5.2% of girls) and late menarche (>= 16 years, 6.7% of girls) were both associated with oligomenorrhea (>= 42 days) in adulthood, 29% and 11%, vs. 5% for normal menarche (11-15 years), p =.004. Early menarche was characterized by high childhood BMI (LS mean +/- SE: 21.2+1.0 kg/m(2)) and by high childhood and adult MetS (15%, 36%). Girls with late menarche had the lowest childhood BMI (18.1 +/- 1.0), no childhood MetS, and the highest adult MetS (47%). Increasing age at menarche was associated with uniformly decreasing childhood BMI and MetS, but with a U-shaped pattern of BMI (p =.05), MetS (p =.008), and oligomenorrhea (p =.02) in adulthood. Change to MetS from median ages 13 to 38 was associated with early-late menarche (OR = 3.11, 95% CI 1.37-7.07, p =.007). MetS in adulthood was associated with childhood MetS (OR = 8.03, 95% CI 2.57-25.08, p =.0003) and with early-late menarche (OR =3.43, 95% CI 1.44-8.15, p =.005).Conclusions. Menarche age had a curvilinear ('U' shaped) relationship with MetS and oligomenorrhea in adulthood. Late menarche and early menarche are risk factors for adult oligomenorrhea, MetS, and cardiometabolic abnormalities. Girls with early (<= age 10) and with late menarche (>= 16) represent a group at high risk for adult cardiometabolic abnormalities and oligomenorrhea that is easily identifiable by physicians. (C) 2013 Elsevier Inc. All rights reserved.

Background Goals for cardiovascular (CV) disease prevention were set by the American Heart Association in 2010 for the concept of CV health. Ideal CV health is defined by 7 CV health metrics: blood pressure, glucose, cholesterol, body mass index, and physical activity on recommended levels; nonsmoking; and a healthy diet. We studied the prevalence of ideal CV health and its associations with ultrasonographically measured carotid intima‐media thickness (cIMT) cross‐sectionally in 5 international populations. Methods and Results Prevalence of ideal CV health was assessed among 5785 young adults (age, 36.6±3.2 years) comprising 335 participants from the Minneapolis Childhood Cohort Studies (Minnesota), 723 from the Princeton Follow‐up Study, 981 from the Bogalusa Heart Study (BHS), 1898 from the Cardiovascular Risk in Young Finns Study (YFS), and 1848 from the Childhood Determinants of Adult Health Study (CDAH). Only 1% of the participants had all 7 ideal CV health metrics. The number of ideal CV health metrics associated inversely with cIMT in the 4 cohorts in which cIMT was available: for each additional ideal CV health metric, cIMT was 12.7 μm thinner in Minnesota (P=0.0002), 9.1 μm thinner in BHS (P=0.05), 10.4 μm thinner in YFS (P<0.0001), and 3.4 μm thinner in CDAH (P=0.03). Conclusions The number of ideal CV health metrics was inversely associated with cIMT in the cohorts in which cIMT was available, indicating that ideal CV health metrics are associated with vascular health at the population level. Ideal CV health was rare in this large international sample of young adults, emphasizing the need for effective strategies for health promotion.

Background: The American Heart Association recently defined ideal cardiovascular health by simultaneous presence of seven health behaviors and factors. The concept is associated with cardiovascular disease incidence, and cardiovascular disease and all-cause mortality. To effectively promote ideal cardiovascular health already early in life, childhood factors predicting future ideal cardiovascular health should be investigated. Our aim was thus to comprehensively explore childhood determinants of adult ideal cardiovascular health in population based cohorts from three continents.Methods: The sample comprised a total of 4409 participants aged 3-19 years at baseline fromthe Cardiovascular Risk in Young Finns Study (YFS; N = 1883) fromFinland, Childhood Determinants of AdultHealth Study (CDAH; N = 1803) from Australia and Princeton Follow-up Study (PFS; N = 723) from the United States. Participants were re-examined 19-31 years later when aged 30-48 years.Results: In multivariable analyses, independent childhood predictors of adult ideal cardiovascular health were family socioeconomic status (P b 0.01; direct association) andBMI (P b 0.001; inverse association) in all cohorts. In addition, blood pressure (P = 0.007), LDL-cholesterol (P b 0.001) and parental smoking (P = 0.006) in the YFS, and own smoking (P = 0.001) in CDAH were inversely associated with future ideal cardiovascular health.Conclusions: Among several lifestyle and clinical indicators studied, higher family socioeconomic status and nonsmoking (parental/own) in childhood independently predict ideal cardiovascular health in adulthood. As atherosclerotic cardiovascular diseases are rooted in childhood, our findings suggest that special attention could be paid to childrenwho are fromlowsocioeconomic status families, and who smoke orwhose parents smoke, to prevent cardiovascular disease morbidity and mortality. c 2013 Elsevier Ireland Ltd. All rights reserved.

The prevalence of Class 3 obesity (BMI ≥40 kg/m 2 ) has more than doubled in the past 25 years. In a 14‐year prospective study from age 10 to 24 of a biracial schoolgirl cohort (293 black, 256 white), we assessed childhood correlates of Class 3 BMI at age 24. Of 42 girls with Class 3 BMI at age 24, 36 (86%) were black. By logistic regression, significant explanatory variables of Class 3 BMI at age 24 included top decile waist circumference at age 11 (odds ratio (OR) 5.7, 95% confidence interval (CI) 2.3–13.9, P = 0.0002), age 10 BMI ≥ the Center for Disease Control (CDC) 2000 top 15% (OR 7.0, 95% CI 2.5–19.3, P = 0.0002), and a three‐way interaction between race, childhood insulin, and average caloric intake from age 10 to age 19 (for each unit increase, OR 1.7 95% CI 1.3–2.2, P = 0.0003). Age 10 BMI, age 11 waist circumference, and interaction of race, childhood insulin, and childhood caloric intake predict Class 3 obesity in young adulthood, facilitating childhood identification of girls at high risk for developing Class 3 obesity.

Pediatric risk factors predict adult cardiovascular disease (CVD) and type 2 diabetes (T2DM), but whether they predict events independently of adult risk factors is not fully known.

Objective To evaluate children's cardiovascular disease (CVD) risk factors as predictors of parents' subsequent CVD, type 2 diabetes mellitus (T2DM), and high blood pressure (HBP).Study design We conducted a 26-year prospective follow-up of 852 5 -to 19-year-old black and white schoolchildren (mean age, 12 years; Lipid Research Clinics, 1973-8), and parents (mean age, 40 years) from 519 families in Princeton Schools, Cincinnati, Ohio. Schoolchildren were reassessed in the Princeton Follow-up study 19992003 at mean age 39 years; CVD, T2DM, and HBP history of their 1038 parents were reassessed by mean age 66 years. We assessed relationships of childhood risk factors with parental CVD, T2DM, and HBP. Child-probands identified with triglyceride (TG) levels, blood pressure, low-density lipoprotein cholesterol levels, body mass index (BMI), and glucose level greater than and high-density lipoprotein cholesterol levels less than established cutoff points.Results Pediatric HBP (P = .006) and low high-density lipoprotein cholesterol (P = .018) were predictive of parental CVD at age <= 50 years. Pediatric HBP (P = .02) and high TG (P = .03) were predictive of parental CVD at age <= 60 years. Pediatric high TG (P = .009) and high low-density lipoprotein cholesterol (P = .04) were predictive of parental CVD by age 66 years. Pediatric high BMI (P = .0006) were predictive of parental T2DM. Pediatric high BMI (P = .003) and black race (P = .004) were predictive of parental HBP.Conclusions Pediatric risk factors identify families with parents at increased risk for CVD, T2DM, and HBP, emphasizing the usefulness of the child as proband. (J Pediatr 2012;160:590-7).

The objective was to assess whether pediatric risk factors predict cardiovascular disease (CVD), impaired fasting glucose (IFG) + type 2 diabetes mellitus (T2DM), and high blood pressure (HBP) in young adulthood. We performed a prospective follow-up of 909 public-parochial suburban schoolchildren first studied at ages 6 to 18 years and 26 years later at a mean age of 38 years. Pediatric triglycerides (TGs), blood pressure, low-density lipoprotein cholesterol, body mass index, and glucose above and high-density lipoprotein cholesterol below established pediatric cutoffs, along with race, cigarette smoking, family history of CVD, T2DM, and HBP, were assessed as determinants of young adult CVD, a composite variable including IFG + T2DM and HBP. By stepwise logistic regression, adult CVD (19 yes, 862 no) was associated with pediatric high TG (odds ratio [OR], 5.85; 95% confidence interval [CI], 2.3-14.7). High TG in pediatric probands with young adult CVD was familial and was associated with early CVD in their high-TG parents. Adult IFG + T2DM (114 yes, 535 no) was associated with parental T2DM (OR, 2.2; 95% CI, 1.38-3.6), high childhood glucose (OR, 4.43; 95% CI, 2-9.7), and childhood cigarette smoking (OR, 1.64; 95% CI, 1.03-2.61). Adult HBP (133 yes, 475 no) was associated with pediatric high body mass index (OR, 2.7; 95% CI, 1.7-4.3) and HBP (OR, 2.5; 95% CI, 1.5-4.3). Pediatric risk factors are significantly, independently related to young adult CVD, IFG + T2DM, and HBP. Identification of pediatric risk factors for CVD, IFG + T2DM, and HBP facilitates initiation of primary prevention programs to reduce development of adult CVD, IFG + T2DM, and HBP.

This is a consortium of large children's cohorts that contain measurements of major cardiovascular disease (CVD) risk factors in childhood and had the ability to follow those cohorts into adulthood. The purpose of this consortium is to enable the pooling of data to increase power, most importantly for the follow-up of CVD events in adulthood. Within the consortium, we hope to be able to obtain data on the independent effects of childhood and early adult levels of CVD risk factors on subsequent CVD occurrence.

See related article, p 201The article by Li et al1Li C. Ford E.S. McBride P.E. Kwiterovitch P.O. McCrinle B.W. Gidding S.S. Non-high-density lipoprotein cholesterol concentration is associated with the metabolic syndrome among US youth aged 12-19 years.J Pediatr. 2011; 158: 201-207Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar in this issue of The Journal presents interesting new data on the cross-sectional association of non–high-density lipoprotein (HDL)-cholesterol (HDL-C) (low-density lipoprotein [LDL]- and very low-density lipoprotein [VLDL]-cholesterol [LDL-C and VLDL-C]) with the metabolic syndrome (MetS) in US youth. This finding raises as many issues as it settles but should guide future analyses into new directions. The data come from the 1999-2004 National Health and Nutrition Survey, with the cohort including a population-based sample of 2734 adolescents ages 12 to 19 years. Because there is no single definition for MetS for this age group, the authors used four different definitions: (1) the Third Report of the National Cholesterol Education program Expert Panel (NCEP III); (2) the NCEP II adapted for children and adolescents (NCEP III Peds); (3) the International Diabetes Federation (IDF) for adults; and (4) the IDF adapted for children and adolescents (IDF-Peds). These definitions were carefully laid out and different cutoffs of non–HDL-C used. See related article, p 201 For each MetS definition, a ROC curve was generated from a logistic model, which used non–HDL-C to predict MetS. The optimum cutoff for non–HDL-C was determined using the Youdan index. Then, for the optimum cutoff as well as 70th and 90th percentiles of non–HDL-C, the sensitivities and specificities of MetS were calculated according to each MetS definition. Results differed across cutoffs and definitions, but consistently showed that non–HDL-C was a significant predictor of concurrent MetS. A central link in the non-HDL-C–MetS chain is insulin resistance (IR). The spark that ignited interest in MetS was Reaven’s Banting Lecture in 1988,2Reaven G.M. Banting lecture 1988: Role of insulin resistance in human disease.Diabetes. 1988; 37: 1595-1607Crossref PubMed Google Scholar in which he argued forcefully for a central role of IR and resulting hyperinsulinemia in both type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Stating that IR is necessary but not sufficient for development of T2DM, Reaven2Reaven G.M. Banting lecture 1988: Role of insulin resistance in human disease.Diabetes. 1988; 37: 1595-1607Crossref PubMed Google Scholar discussed the ways individuals respond to IR, concluding that the “fact that an insulin-resistant subject may not become diabetic does not mean that they suffer no untoward consequences (emphasis added).” Reaven then discussed some of the “untoward” sequelae of IR beyond the inability of the ß-cell to compensate by producing more insulin (ie, diabetes), weaving together several risk factors including hypertension, low HDL-C, and high triglyceride (TG) that are associated with IR-hyperinsulinemia and hyperglycemic states.2Reaven G.M. Banting lecture 1988: Role of insulin resistance in human disease.Diabetes. 1988; 37: 1595-1607Crossref PubMed Google Scholar He concluded “…there is a series of related variables—syndrome X—that tends to occur in the same individual and may be of enormous importance in the genesis of CAD.” He brought his argument to a close by pointing out the association of IR with obesity and lack of physical activity.2Reaven G.M. Banting lecture 1988: Role of insulin resistance in human disease.Diabetes. 1988; 37: 1595-1607Crossref PubMed Google Scholar Thus, based on a foundation of IR-hyperinsulinemia,3Reaven G.M. Insulin resistance, the insulin resistance syndrome, and cardiovascular disease.Panminerva Med. 2005; 47: 201-210PubMed Google Scholar we have here all the essential elements of what became the MetS, an alternative physiological model for development of CVD without recourse to LDL-C, one that supplemented and extended the original model. From Reaven’s 1988 Banting Lecture2Reaven G.M. Banting lecture 1988: Role of insulin resistance in human disease.Diabetes. 1988; 37: 1595-1607Crossref PubMed Google Scholar onward, there has been a steady stream of articles focusing on the conjoint occurrence of the MetS factors in people with or at risk of T2DM and CVD, noting among other things that although the relative risk of CVD associated with high LDL-C is significant, most people with incident CVD do not have high LDL-C, defined by the upper 5 or 10 percentiles. The findings of Li et al suggest a kind of “unified field theory,” pulling together the standard lipid model (LDL-C–apoB 100) with an apoB48 model, with dense LDL and linking the two models together. The strong association of fasting non–HDL-C concentration with MetS among US youth described by Li et al1Li C. Ford E.S. McBride P.E. Kwiterovitch P.O. McCrinle B.W. Gidding S.S. Non-high-density lipoprotein cholesterol concentration is associated with the metabolic syndrome among US youth aged 12-19 years.J Pediatr. 2011; 158: 201-207Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar makes sense physiologically, given the underlying association of IR-hyperinsulinemia (IR) with MetS3Reaven G.M. Insulin resistance, the insulin resistance syndrome, and cardiovascular disease.Panminerva Med. 2005; 47: 201-210PubMed Google Scholar, 4Li C. Ford E.S. Meng Y.X. Mokdad A.H. Reaven G.M. Does the association of the triglyceride to high-density lipoprotein cholesterol ratio with fasting serum insulin differ by race/ethnicity?.Cardiovasc Diabetol. 2008; 7: 4Crossref PubMed Scopus (174) Google Scholar and with overproduction of VLDL cholesterol, a major component of non–HDL-C.5Adiels M. Olofsson S.O. Taskinen M.R. Boren J. Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome.Arterioscler Thromb Vasc Biol. 2008; 28: 1225-1236Crossref PubMed Scopus (580) Google Scholar IR and resulting hyperinsulinemia are associated with all of the major components of the MetS, glucose, triglycerides, HDL-C, obesity and centripetal obesity, and hypertension.6Morrison J.A. Ford E.S. Steinberger J. The pediatric metabolic syndrome.Minerva Med. 2008; 99: 269-287PubMed Google Scholar IR is also associated with an increased concentration of dense LDL particles, (rich in apoB 100 and relatively lipid poor), which is prospectively associated with both T2DM and CVD.7Lemieux I. Pascot A. Couillard C. Lamarche B. Tchernof A. Almeras N. et al.Hypertriglyceridemic waist: a marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men?.Circulation. 2000; 102: 179-184Crossref PubMed Scopus (808) Google Scholar, 8Eckel R.H. Mechanisms of the components of the metabolic syndrome that predispose to diabetes and atherosclerotic CVD.Proc Nutr Soc. 2007; 66: 82-95Crossref PubMed Scopus (42) Google Scholar, 9Reaven G.M. Chen Y.D. Jeppesen J. Maheux P. Krauss R.M. Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles.J Clin Invest. 1993; 92: 141-146Crossref PubMed Scopus (630) Google Scholar IR also associates with increased apo B 48 (chylomicrons and VLDL-C), involving increased TG, and is inversely associated with HDL-C.3Reaven G.M. Insulin resistance, the insulin resistance syndrome, and cardiovascular disease.Panminerva Med. 2005; 47: 201-210PubMed Google Scholar The TG/HDL-C ratio appears to be a marker for hyperinsulinemia.4Li C. Ford E.S. Meng Y.X. Mokdad A.H. Reaven G.M. Does the association of the triglyceride to high-density lipoprotein cholesterol ratio with fasting serum insulin differ by race/ethnicity?.Cardiovasc Diabetol. 2008; 7: 4Crossref PubMed Scopus (174) Google Scholar Fasting serum insulin independently and uniformly improves the prediction of CVD status beyond traditional risk factors and lipid variables in patients referred for treatment of hyperlipidemia.10Glueck C.J. Lang J.E. Tracy T. Sieve-Smith L. Wang P. Contribution of fasting hyperinsulinemia to prediction of atherosclerotic cardiovascular disease status in 293 hyperlipidemic patients.Metabolism. 1999; 48: 1437-1444Abstract Full Text PDF PubMed Scopus (19) Google Scholar IR is an independent risk factor for future CVD,11Bonora E. Formentini G. Calcaterra F. Lombardi S. Marini F. Zenari L. et al.HOMA-estimated insulin resistance is an independent predictor of cardiovascular disease in type 2 diabetic subjects: prospective data from the Verona Diabetes Complications Study.Diabetes Care. 2002; 25: 1135-1141Crossref PubMed Scopus (479) Google Scholar thus explaining to some degree the occurrence of CVD in patients with “normal” LDL-C. Childhood MetS and its separate components are associated with T2DM in young adulthood.12Franks P.W. Hanson R.L. Knowler W.C. Moffett C. Enos G. Infante A.M. et al.Childhood predictors of young-onset type 2 diabetes.Diabetes. 2007; 56: 2964-2972Crossref PubMed Scopus (125) Google Scholar, 13Morrison J.A. Friedman L.A. Wang P. Glueck C.J. Metabolic syndrome in childhood predicts adult metabolic syndrome and type 2 diabetes mellitus 25 to 30 years later.J Pediatr. 2008; 152: 201-206Abstract Full Text Full Text PDF PubMed Scopus (507) Google Scholar Pre-teen IR and insulin level and rapidly increasing IR during adolescence identify girls who are at greater risk of future impaired fasting glucose and T2DM.14Morrison J.A. Glueck C.J. Horn P.S. Schreiber G.B. Wang P. Pre-teen insulin resistance predicts weight gain, impaired fasting glucose, and type 2 diabetes at age 18-19 y: a 10-y prospective study of black and white girls.Am J Clin Nutr. 2008; 88: 778-788PubMed Scopus (70) Google Scholar In addition, pre-teen IR, interacting with high fat diets, identifies adolescent girls who are at greater risk of weight gain.15Morrison J.A. Glueck C.J. Wang P. Preteen insulin levels interact with caloric intake to predict increases in obesity at ages 18 to 19 years: a 10-year prospective study of black and white girls.Metabolism. 2010; 59: 718-727Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Ten-year increases in body mass index from ages 8-9 to 18-19 are significantly and independently associated with a three-way interaction between ages 9-10 insulin, adolescent caloric intake, and race (higher in black girls).15Morrison J.A. Glueck C.J. Wang P. Preteen insulin levels interact with caloric intake to predict increases in obesity at ages 18 to 19 years: a 10-year prospective study of black and white girls.Metabolism. 2010; 59: 718-727Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Hyperinsulinemia and MetS at mean age 10 years in black and white schoolgirls predict development of impaired fasting glucose and T2DM by age 24.16Morrison J.A. Glueck C.J. Umar M. Daniels S. Dolan L.M. Wang P. Hyperinsulinemia and metabolic syndrome at mean age of 10 years in black and white schoolgirls and development of impaired fasting glucose and type 2 diabetes mellitus by mean age of 24 years.Metabolism. 2010; (Epub ahead of print)Google Scholar Childhood insulin Z scores and insulin Z scores 15 years later are correlated (r = 0.30, P < .001).16Morrison J.A. Glueck C.J. Umar M. Daniels S. Dolan L.M. Wang P. Hyperinsulinemia and metabolic syndrome at mean age of 10 years in black and white schoolgirls and development of impaired fasting glucose and type 2 diabetes mellitus by mean age of 24 years.Metabolism. 2010; (Epub ahead of print)Google Scholar In a 15-year prospective study of schoolgirls, childhood insulin (partial R2 = 40% was a major independent predictor for average insulin Z score during the 15-year follow-up).17Morrison J.A. Glueck C.J. Daniels S. Wang P. Determinants of persistent obesity and hyperinsulinemia in a biracial cohort: a 15-year prospective study of schoolgirls.J Pediatr. 2010; (Epub ahead of print)Google Scholar Childhood insulin tracks into young adulthood,16Morrison J.A. Glueck C.J. Umar M. Daniels S. Dolan L.M. Wang P. Hyperinsulinemia and metabolic syndrome at mean age of 10 years in black and white schoolgirls and development of impaired fasting glucose and type 2 diabetes mellitus by mean age of 24 years.Metabolism. 2010; (Epub ahead of print)Google Scholar and it would be expected that IR-hyperinsulinemia’s effect on the components of MetS would persist from childhood into young adulthood. Thus, MetS in childhood predicts adult MetS and T2DM 25 to 30 years later in adulthood.13Morrison J.A. Friedman L.A. Wang P. Glueck C.J. Metabolic syndrome in childhood predicts adult metabolic syndrome and type 2 diabetes mellitus 25 to 30 years later.J Pediatr. 2008; 152: 201-206Abstract Full Text Full Text PDF PubMed Scopus (507) Google Scholar The pediatric link between MetS and non-HDL-C cholesterol, as identified by Li et al in the current issue of The Journal, may be related both to the association of IR with TG, a major component of MetS, and the role of TG (VLDL-C) as a major component of non-HDL-C and an independent risk factor for CVD. We have recently assessed the relationship of childhood TG to adult cardiovascular events in the Princeton Follow-up Study, a prospective 22- to 31-year follow-up studies (1998 to 2003) in former schoolchildren first studied in 1973 to 1976.18Morrison J.A. Glueck C.J. Horn P.S. Yeramaneni S. Wang P. Pediatric triglycerides predict cardiovascular disease events in the fourth to fifth decade of life.Metabolism. 2009; 58: 1277-1284Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar The major novel finding of this study was that childhood TG was consistently and independently associated with young adult CVD. The distributions of both childhood and adult TG were shifted to higher levels in cases compared with control subjects.18Morrison J.A. Glueck C.J. Horn P.S. Yeramaneni S. Wang P. Pediatric triglycerides predict cardiovascular disease events in the fourth to fifth decade of life.Metabolism. 2009; 58: 1277-1284Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Childhood TG level was a significant, independent explanatory variable for young adult CVD hazard (hazard ratio, 5.35; 95% confidence interval, 1.69 to 20) (for each 1-unit increase in natural logarithm scale), along with adult T2DM (hazard ratio, 19.4; 95% confidence interval, 4.24 to 114.2). These findings are congruent with studies in adults where nonfasting TG19Bansal S. Buring J.E. Rifai N. Mora S. Sacks F.M. Ridker P.M. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women.JAMA. 2007; 298: 309-316Crossref PubMed Scopus (1289) Google Scholar, 20McBride P.E. Triglycerides and risk for coronary heart disease.JAMA. 2007; 298: 336-338Crossref PubMed Scopus (89) Google Scholar, 21Nordestgaard B.G. Benn M. Schnohr P. Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women.JAMA. 2007; 298: 299-308Crossref PubMed Scopus (1678) Google Scholar and fasting TG19Bansal S. Buring J.E. Rifai N. Mora S. Sacks F.M. Ridker P.M. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women.JAMA. 2007; 298: 309-316Crossref PubMed Scopus (1289) Google Scholar, 22Austin M.A. McKnight B. Edwards K.L. Bradley C.M. McNeely M.J. Psaty B.M. et al.Cardiovascular disease mortality in familial forms of hypertriglyceridemia: a 20-year prospective study.Circulation. 2000; 101: 2777-2782Crossref PubMed Scopus (224) Google Scholar are independent risk factors for CVD. What is needed are prospective studies between pediatric non–HDL-C, TG, IR, MetS, and the development of CVD events and T2DM in adulthood. We have recently assessed relationships of childhood non–HDL-C to adult CVD events in the Princeton Follow-up Study, a prospective 22- to 31-year follow-up of former schoolchildren first studied in 1973 to 1976.18Morrison J.A. Glueck C.J. Horn P.S. Yeramaneni S. Wang P. Pediatric triglycerides predict cardiovascular disease events in the fourth to fifth decade of life.Metabolism. 2009; 58: 1277-1284Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Unlike childhood TG, which was a significant independent correlate of CVD events in adulthood, non–HDL-C was not a significant risk factor for CVD in this cohort at mean age 38.5 years, possibly due to widespread reported use of statins by cohort members. Future research will help to refine our understanding of those relationships. Non–High-Density Lipoprotein Cholesterol Concentration is Associated with the Metabolic Syndrome among US Youth Aged 12-19 YearsThe Journal of PediatricsVol. 158Issue 2PreviewTo test the hypothesis that the concentration of non–high-density lipoprotein cholesterol (non–HDL-C) is associated with the metabolic syndrome (MetS) in youth. Full-Text PDF

To assess the degree of familial clustering of fruit and vegetable consumption (FVC) in adult offspring and their parents 15 to 27 yr after the shared household and its association with BMI, we analyzed data from the Block food frequency questionnaire on 1,450 cohort members of the Princeton Follow‐up Study in a cross‐sectional analysis. BMI was calculated as (kg/m2). Heritability was estimated using a variance components model and genetic and phenotypic correlations were estimated using a multivariate model using SOLAR. Fruit and vegetable consumptions and BMI exhibited significant heritability estimates (h2= 0.26±0.06, 0.32±0.06, 0.46 ±0.06, all p<0.001). Both fruit and vegetable consumptions exhibited significant negative genetic correlations with BMI (ρg = −0.28 ± 0.13 & −0.30 ± 0.13, p<0.05) but the phenotypic correlations of BMI with FVC were not significant. The finding suggested that there is underlying genetic basis to eating fruits and vegetables and that this also in part influences the underlying basis of BMI. Further studies need to explore what specific genes are involved in this genetic association between FVC and BMI.