Severity of the metabolic syndrome as a predictor of type 2 diabetes between childhood and adulthood: the Princeton Lipid Research Cohort Study.

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.

Adolescent and young adult female determinants of visceral adipose tissue at ages 26-28 years.

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.

Adolescent oligomenorrhea (age 14-19) tracks into the third decade of life (age 20-28) and predicts increased cardiovascular risk factors and metabolic syndrome.

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 ≥42 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.

Genetic architecture of lipid traits changes over time and differs by race: Princeton Lipid Follow-up Study.

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.

Childhood lifestyle and clinical determinants of adult ideal cardiovascular health: the Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Princeton Follow-Up Study.

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 from the Cardiovascular Risk in Young Finns Study (YFS; N = 1883) from Finland, Childhood Determinants of Adult Health 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 < 0.01; direct association) and BMI (P < 0.001; inverse association) in all cohorts. In addition, blood pressure (P = 0.007), LDL-cholesterol (P < 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 non-smoking (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 children who are from low socioeconomic status families, and who smoke or whose parents smoke, to prevent cardiovascular disease morbidity and mortality.

Early and late menarche are associated with oligomenorrhea and predict metabolic syndrome 26 years later.

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/m2) 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.

Ideal cardiovascular health in young adult populations from the United States, Finland, and Australia and its association with cIMT: the International Childhood Cardiovascular Cohort Consortium.

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.

Cohort Profile: the international childhood cardiovascular cohort (i3C) consortium.

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.

Risk factors for cardiovascular disease and type 2 diabetes retained from childhood to adulthood predict adult outcomes: the Princeton LRC Follow-up Study.

BACKGROUND: 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: Assess whether risk factors for CVD and T2DM retained from childhood to adulthood predict CVD and T2DM in young adulthood. STUDY DESIGN: 770 schoolchildren, ages 5-20 (mean age 12), 26-yr prospective follow-up. We categorized childhood and adult risk factors and 26-year changes (triglycerides [TG], LDL cholesterol, BMI, blood pressure [BP] and glucose ≥, and HDL cholesterol < pediatric and young adult cutoffs). These risk factors and race, cigarette smoking, and family history of CVD and T2DM were assessed as predictors of CVD and T2DM at mean age 38. RESULTS: Children who had high TG and retained high TG as adults had increased CVD events as adults (p = .0005). Children who had normal BMI and retained normal BMI as adults had reduced CVD events as adults (p = .02). Children who had high BP or high TG and retained these as adults had increased T2DM as adults (p = .0006, p = .003). CONCLUSIONS: Risk factors for CVD and T2DM retained from childhood to adulthood predict CVD and T2DM in young adulthood and support universal childhood screening.

Determinants of ApoB, ApoA1, and the ApoB/ApoA1 ratio in healthy schoolgirls, prospectively studied from mean ages 10 to 19 years: the Cincinnati National Growth and Health Study.

The objectives were to prospectively assess determinants of apolipoproteins B (ApoB), A1 (ApoA1), and the ApoB/ApoA1 ratio in 797 healthy black and white schoolgirls from mean ages 10 to 19. There was prospective 9-year follow-up, with measures of ApoB at mean ages 10, 12, 14, 16 and 19, ApoA1 at mean ages 12, 14, 16, and 19, and assessment of annual reports of delayed menstrual cyclicity (≥42 days) from ages 14 to 19. Studies of 402 black and 395 white healthy schoolgirls were done in public and private schools, in urban and suburban Cincinnati. Black girls had lower ApoB, higher ApoA1, and lower ApoB/ApoA1. SHBG at age 14 in white and black girls was inversely correlated with the ApoB/ApoA1. At age 19, ≥3 annual reports of menstrual delay ≥42 days and metabolic syndrome were associated with higher ApoB and a higher ApoB/ApoA1 ratio. From ages 14 to 19, BMI and TG were independently positively associated with ApoB. Menstrual cyclicity ≥42 days, metabolic syndrome, BMI, and TG were independently positively associated with ApoB/ApoA1 ratios, while black race was negatively associated. The atherogenic ApoB/ApoA1 ratio from ages 14 to 19 is lower in black girls, and positively associated with hyperandrogenism, menstrual cyclicity ≥42 days, BMI, TG, and the metabolic syndrome, facilitating an adolescent approach to primary prevention of cardiovascular disease.

The child as proband for future parental cardiometabolic disease: the 26-year prospective Princeton Lipid Research Clinics Follow-up Study.

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 1999-2003 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.

Race, childhood insulin, childhood caloric intake, and class 3 obesity at age 24: 14-year prospective study of schoolgirls.

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.

Childhood risk factors predict cardiovascular disease, impaired fasting glucose plus type 2 diabetes mellitus, and high blood pressure 26 years later at a mean age of 38 years: the Princeton-lipid research clinics follow-up study.

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.

Percent body fat and chronic disease risk factors in U.S. children and youth.

BACKGROUND: The dramatic increase in pediatric obesity has renewed interest in accurate methods and screening indexes for identifying at-risk children and youth. Whether age-specific standards are needed is a factor that remains uncertain. PURPOSE: This study was designed to describe the age-specific fatness-risk factor relationship in boys and girls across a wide age range. METHODS: Data were from 12,279 white, black, and Mexican-American children and adolescents from the National Health and Nutritional Examination Surveys (NHANES) III (1998-1994) and IV (1999-2004). Children were grouped based on percent fat, estimated from subscapular and triceps skinfolds, and the age-specific relationships between percent fat and chronic disease risk factors (e.g., blood pressure, lipids and lipoprotein levels, glucose, insulin, and circulating C-reactive protein levels) were described in boys and girls, aged 6-18 years. RESULTS: Percent fat was significantly related to risk factor levels. At higher levels of percent fat, the prevalence of adverse cardiovascular disease risk factors was higher, particularly above 20% fat in boys and above 30% fat in girls. In boys and girls, the interaction term age by percent fat was a significant predictor of risk factors, whereas the percent fat by race interaction term was nonsignificant. CONCLUSIONS: The results demonstrate a strong relationship between chronic disease risk factors and percent fat in children and youth that varies by age in boys and girls.

Ramifications of adolescent menstrual cycles ≥42 days in young adults.

OBJECTIVE: To determine to what degree annual reports from ages 14 to 19 years of menstrual cycles ≥42 days would be associated with increased body mass index (BMI), waist circumference, glucose, insulin, and homeostasis model assessment insulin resistance (HOMA-IR) at ages 14-25 years. DESIGN: Prospective 11-year follow-up from ages 14 to 25 years. SETTING: Urban-suburban schools, post-high school. PATIENT(S): A total of 370 schoolgirls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): BMI, waist, insulin, glucose, HOMA-IR. RESULT(S): From ages 14 to 19 years, 269 girls had 0/6 annual reports of menstrual cycles ≥42 days, 74 had 1, 19 had 2, and 8 had ≥3. Among these four categories, girls with ≥3 annual reports had highest free T and DHEAS at age 14, highest BMI and waist at ages 14, 19, and 25, highest insulin at age 25, and highest glucose and HOMA-IR at age 24 years. The number of annual reports of menstrual cycles ≥42 days was positively related to change in BMI and waist and inversely with change in high-density lipoprotein cholesterol from ages 14 to 25 years. CONCLUSION(S): Three or more annual reports of menstrual cycles ≥42 days during ages 14-19 are associated with high BMI, waist circumference, insulin, glucose, and HOMA-IR at ages 14-25 years.

Sex hormone-binding globulin, oligomenorrhea, polycystic ovary syndrome, and childhood insulin at age 14 years predict metabolic syndrome and class III obesity at age 24 years.

OBJECTIVE: We hypothesized that oligomenorrhea (menstrual cyclicity ≥42 days), hyperandrogenism, low levels of sex hormone-binding globulin (SHBG), childhood insulin, and metabolic syndrome (MetS) at age 14 years would predict MetS and class III obesity (body mass index ≥40 kg/m(2)) at age 24 years. STUDY DESIGN: In this prospective study of schoolgirls, at age 14 years, the girls were categorized as regularly cycling (n = 375), oligomenorrheic (n = 18), or oligomenorrhea plus biochemical hyperandrogenism (polycystic ovary syndrome [PCOS]; n = 12), together designated PCOS. RESULTS: Significant explanatory variables for MetS at age 24 years included childhood insulin, MetS, and PCOS category (all positive) and SHBG (negative) at age 14 years. Using categorical data, top decile of childhood insulin, MetS at age 14, bottom decile of SHBG, and PCOS category were significant positive predictors for MetS at age 24. SHBG (negative), black race (positive), and oligomenorrhea (positive) were significant explanatory variables for class III obesity at age 24. Using categorical data, black race, MetS at age 14, bottom decile of SHBG, PCOS category, and top decile of childhood insulin were positive explanatory variables for class III obesity at age 24 years. CONCLUSIONS: Oligomenorrhea, PCOS (a subcohort of oligomenorrhea), hyperandrogenism, low SHBG, MetS, and childhood insulin at age 14 years may represent a critical, reversible pathway for the development of MetS and class III obesity in young adulthood.

Adolescent oligomenorrhea in a biracial schoolgirl cohort: a simple clinical parameter predicting impaired fasting glucose plus type 2 diabetes mellitus, insulin, glucose, insulin resistance, and centripetal obesity from age 19 to 25 years.

We hypothesized that adolescent oligomenorrhea (ages 14-19) would independently predict impaired fasting glucose (IFG; ≥110 to <126 mg/dL) plus type 2 diabetes mellitus (T2DM; ≥126 mg/dL), insulin and glucose levels, and insulin resistance (IR) in young adulthood (ages 19-25). A prospective 15-year follow-up of 370 schoolgirls starting at age 10 was performed. Age 14 waist circumference was the most important explanatory variable for IFG + T2DM during ages 19 to 24 (P = .002; odds ratio, 1.06; 95% confidence interval, 1.02-1.10), along with oligomenorrhea category from ages 14 to 19 (0, 1, 2, ≥3 reports over 6 years; P = .032; odds ratio, 1.82; 95% confidence interval, 1.05-3.14). Impaired fasting glucose + T2DM at ages 19 to 24 were more common in girls having 1 (6%), 2 (11%), and ≥3 (38%) oligomenorrhea reports from ages 14 to 19 than in girls without oligomenorrhea (3%; P = .0003). Positive explanatory variables (all Ps ≤ .05) for homeostasis model assessment of IR at ages 19 to 24 included age 14 waist (partial R(2) = 30.1%), oligomenorrhea with hyperandrogenism (polycystic ovary syndrome; partial R(2) = 4.1%), black race (3.8%), and oligomenorrhea frequency during ages 14 to 19 (0.8%); sex hormone binding globulin was a negative explanatory variable (0.7%). This is the first prospective study to report an independent association of adolescent oligomenorrhea with young adult IFG + T2DM, with insulin and glucose levels, and with IR. Age 14 waist circumference, oligomenorrhea with hyperandrogenism (polycystic ovary syndrome), black race, oligomenorrhea frequency at ages 14 to 19, and age 14 sex hormone binding globulin were independently associated with IR at ages 19 to 24, potentially facilitating primary prevention of IFG, T2DM, and hyperinsulinemia.

Paradoxically high adiponectin in obese 16-year-old girls protects against appearance of the metabolic syndrome and its components seven years later.

OBJECTIVE: To evaluate the relationships of adiponectin levels at age 16 years in obese schoolgirls to metabolic syndrome and its components at age 23 years. STUDY DESIGN: Seven-year prospective study of 381 females. RESULTS: In 144 white and 129 black non-obese 16-year old girls (body mass index < 24.6 kg/m(2)), race-specific median adiponectin levels (white 12 mg/L, black 11) was used to identify paradoxically high adiponectin levels in obese girls. Of 34 white and 74 black obese girls, 12 (35%) and 19 (26%) had paradoxically high adiponectin levels. In these 108 obese girls, adiponectin levels at age 16 years independently predicted high-density lipoprotein cholesterol (positive) and waist (negative), insulin (negative), and glucose (negative) at age 23 years; paradoxically high adiponectin levels at age 16 years was a negative independent predictor for waist, homeostatic model assessment-insulin resistance, and for the number of abnormal components of the metabolic syndrome at age 23 years. In 31 pairs of obese girls with and without paradoxically high adiponectin levels, matched by race and age 16 body mass index, adiponectin levels at age 16 years was a negative predictor for the number of abnormal metabolic syndrome components at age 23 years. CONCLUSION: Paradoxically high adiponectin levels in obese 16 year old girls protects against metabolic syndrome and its components at age 23 years.