Stephanie L. Filipp

Examining trends in prediabetes and its relationship with the metabolic syndrome in US adolescents, 1999–2014

AimsWe sought to investigate temporal trends in prediabetes prevalence among US adolescents using two definitions and evaluate relationships with obesity and a MetS-severity score.MethodsWe evaluated data from 5418 non-Hispanic white, non-Hispanic black, and Hispanic adolescents aged 12–19 participating in the National Health and Nutrition Examination Survey 1999–2014 with complete data regarding MetS and hemoglobin A1c (HbA1c). Prediabetes status was defined by American Diabetes Association (ADA) criteria: fasting glucose 100–125 mg/dL or HbA1c 5.7%–6.4%. MetS severity was assessed with a MetS-severity Z-score.ResultsPrevalence of prediabetes as defined by HbA1c abnormalities significantly increased from 1999–2014, while prevalence of prediabetes as defined by fasting glucose abnormalities showed no significant temporal trend. There were variations in these trends across different racial/ethnic groups. MetS Z-score was overall more strongly correlated with HbA1c, fasting insulin, and the homeostasis model of insulin resistance than was BMI Z-score. These correlations were true in each racial/ethnic group with the exception that in non-Hispanic white adolescents, in whom the MetS Z-score was not significantly correlated with HbA1c measurements.ConclusionWe found conflicting findings of temporal trends of US adolescent prediabetes prevalence based on the ADA’s prediabetes criteria. The increasing prevalence of prediabetes by HbA1c assessment is concerning and raises the urgency for increased awareness and appropriate measures of prediabetes status among physicians and patients.

Geographical variation in the prevalence of obesity, metabolic syndrome, and diabetes among US adults

Cardiovascular disease (CVD) and type 2 diabetes remain significant public health concerns. Targeting of prevention efforts by geographical location has been suggested by the Institute of Medicine to coincide with the presence of area-based risk. The metabolic syndrome (MetS) is a stronger risk factor than is obesity for the prediction of future CVD and diabetes, yet its prevalence has not previously been described geographically. Our objective is to determine geographical variation in the prevalence of obesity, MetS, and diabetes among US adults. We assessed the prevalence of obesity, MetS, and diabetes by US census division, and the prevalence of obesity, MetS, and diabetes for each sex and racial/ethnic group by US region among 9826 US non-Hispanic white, non-Hispanic black, and Hispanic adults aged 20–65 years participating in the National Health and Nutrition Examination Survey 1999–2014. We also compared a sex- and race/ethnicity-specific MetS severity score by geographical area. The prevalence of obesity, MetS, and diabetes varied by US census division and region, with overall similarity by geographical area in the prevalence of each of these conditions. The prevalence of MetS was particularly high (≥35%) in the West North Central, West South Central, and East South Central and low (30%) in the Pacific, New England, and Mid-Atlantic divisions. Some of the geographical variation appeared due to differences among non-Hispanic white females, who had a high prevalence of MetS (>32%) in the Midwest and South and a low prevalence of MetS (24%) in the West and Northeast. Geographical differences in MetS imply variation in the risk for future CVD and diabetes, with more elevated risk in the center of the United States. As MetS is a stronger risk factor for prediction of CVD and T2DM than is obesity, these differences are potentially important for prompting public health efforts toward surveillance and prevention in high-risk areas.

Longitudinal Associations of Metabolic Syndrome Severity Between Childhood and Young Adulthood: The Bogalusa Heart Study

BACKGROUND Childhood metabolic syndrome (MetS) is associated with insulin resistance and increased risk for later development of type 2 diabetes (T2DM) and cardiovascular disease (CVD). In using MetS severity z-scores, our objective was to assess longitudinal associations in MetS severity, fasting insulin levels as a sign of insulin resistance and risk for T2DM, and uric acid levels as a biomarker of oxidative stress leading to CVD. METHODS We used linear regression to analyze longitudinal data from 285 white and black participants from the Bogalusa Heart Study evaluated at baseline at ages 5-19 and as young adults after a mean of 12.0 years follow-up. We assessed correlations between childhood MetS severity and young-adult MetS severity, fasting insulin, and uric acid levels, both overall and by sex- and racial subgroups. RESULTS Overall, childhood MetS z-scores were positively associated with young-adult MetS z-scores (r = 0.52), insulin (r = 0.34), and uric acid (r = 0.28) (all P < 0.001). These associations were consistent across all sex- and racial subgroups, except for young adult uric acid in white males in which childhood MetS-z was not associated (r = 0.15, P = 0.243). There was a strong cross-sectional association of young-adult MetS z-scores with insulin (r = 0.70) and uric acid (r = 0.57) (both P < 0.001), which was consistent for all sex- and racial subgroups. CONCLUSIONS These positive longitudinal correlations between childhood MetS z-scores and markers of later insulin resistance and oxidative stress suggest long-term durability of risk for CVD and T2DM. This suggests potential for MetS severity to serve as an indicator to monitor for future risk of T2DM and CVD.

Use of BMI as the marker of adiposity in a metabolic syndrome severity score: Derivation and validation in predicting long-term disease outcomes

BACKGROUND Estimates of adiposity in evaluating the metabolic syndrome (MetS) have traditionally utilized measures of waist circumference (WC), whereas body mass index (BMI) is more commonly used clinically. Our objective was to determine if a MetS severity Z-score employing BMI as its measure of adiposity (MetS-Z-BMI) would perform similarly to a WC-based score (MetS-Z-WC) in predicting future disease. METHODS To formulate the MetS-Z-BMI, we performed confirmatory factor analysis on a sex- and race/ethnicity-specific basis on MetS-related data for 6870 adult participants of the National Health and Nutrition Survey 1999-2010. We then validated this score and compared it to MetS-Z-WC in assessing correlations with future coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM) using Cox proportional hazard analysis of 13,094 participants of the Atherosclerosis Risk in Communities study and Jackson Heart Study. RESULTS Loading factors, which represent the relative contribution of each component to the latent MetS factor, were lower for BMI than for WC in formulating the two respective scores (MetS-Z-BMI and MetS-Z-WC). Nevertheless, MetS-Z-BMI and MetS-Z-WC exhibited similar hazard ratios (HR) toward future disease. For each one standard-deviation-unit increase in MetS-Z-BMI, HR for CHD was 1.76 (95% confidence interval [CI]: 1.65, 1.88) and HR for T2DM was 3.39 (CI 3.16, 3.63) (both p < 0.0001). There were no meaningful differences between the MetS-Z-WC and MetS-Z-BMI scores in their associations with future CHD and T2DM. CONCLUSIONS A MetS severity Z-score utilizing BMI as its measure of adiposity operated similarly to a WC-based score in predicting future CHD and T2DM, suggesting overall similarity in MetS-based risk as estimated by both measures of adiposity. This indicates potential clinical usefulness of MetS-Z-BMI in assessing and following MetS-related risk over time.

Metabolic Syndrome Severity and Risk of CKD and Worsened GFR: The Jackson Heart Study

Background/Aims: The metabolic syndrome (MetS), as assessed using dichotomous criteria, is associated with increased risk of future chronic kidney disease (CKD), though this relationship is unclear among African Americans, who have lower risk for MetS but higher risk for CKD. Methods: We performed logistic regression using a sex- and race-specific MetS-severity z-score to assess risk of incident CKD among 2,627 African-American participants of the Jackson Heart Study, assessed at baseline and 8 years later. Based on quartile of baseline MetS severity, we further assessed prevalence of being in the lowest quartile of baseline GFR, the lowest quartile of relative GFR at follow-up, microalbuminuria and incident CKD. Results: Higher MetS-severity was associated with higher prevalence of GFR in the lowest quartile at baseline among males and females. Among African-American females but not males, higher baseline MetS-severity was associated with a higher prevalence of baseline elevations in microabuminuria (p<0.01), steep decline in GFR (p<0.001) and a higher incidence of CKD (p<0.0001). Women in increasing quartiles of baseline MetS-severity exhibited a linear trend toward higher odds of future CKD (p<0.05), with those in the 4th quartile of MetS-severity (compared to the 1st) having an odds ratio of 2.47 (95% confidence interval 1.13, 5.37); no such relationship was seen among men (p value for trend 0.49). Conclusion: MetS-severity exhibited sex-based interactions regarding risk for future GFR deterioration and CKD, with increasing risk in women but not men. These data may have implications for triggering CKD screening among African-American women with higher degrees of MetS-severity.

Use of a Metabolic Syndrome Severity Z Score to Track Risk During Treatment of Prediabetes: An Analysis of the Diabetes Prevention Program

OBJECTIVE We assessed whether changes in metabolic syndrome (MetS) severity during the treatment of prediabetes are associated with reduced risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS We analyzed data from the Diabetes Prevention Program (DPP) for 2,476 adults in 1996–1999 with prediabetes randomized to receive treatment with lifestyle modification, metformin, or placebo for 2–3 years and followed through 2014 for T2DM and CVD outcomes. We calculated effect sizes from baseline in a MetS severity z score (MetS-Z) and the individual MetS components, and assessed relationships between 1-year effect size and incident T2DM and CVD using hazard ratios (HRs) and mediation analysis. RESULTS Baseline MetS-Z and its components were associated with risk of incident T2DM and CVD. During year 1 of intervention, MetS-Z and its components decreased most with lifestyle modification, followed by treatment with metformin and placebo. Risk of T2DM within 1–5 years was most strongly associated with 1-year changes in MetS-Z and waist circumference (both HRs for a 1 SD increase = 1.80), whereas the risk of CVD was associated with a 1-year change in MetS-Z, glucose, and systolic blood pressure. In mediation analyses, the effect of lifestyle modification on T2DM risk was mediated by 1-year changes in MetS-Z, waist circumference, glucose, and triglycerides, whereas the effect of metformin was mediated by MetS-Z and glucose. CONCLUSIONS Changes in these risk indicators of MetS severity during intervention in the DPP reflect altered disease risk and may help in tracking earlier responses to treatment and in motivating patients.