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The metabolic syndrome (MetS) is a group of cardiovascular risk factors that are associated with insulin resistance and are driven by underlying factors, including visceral obesity, systemic inflammation, and cellular dysfunction. These risks increasingly begin in childhood and adolescence and are associated with a high likelihood of future chronic disease in adulthood. Efforts should be made at both recognition of this metabolic risk, screening for potential associated Type 2 diabetes, and targeting affected individuals for appropriate treatment with an emphasis on lifestyle modification. Effective interventions have been linked to reductions in MetS—and in adults, reductions in the severity of MetS have been linked to reduced diabetes and cardiovascular disease.

Cardiovascular disease (CVD) and type 2 diabetes mellitus have their roots in childhood, particularly in obese children and adolescents, raising important opportunities for early lifestyle intervention in at-risk individuals. However, not all obese individuals are at the same risk for disease progression. Accurate screening of obese adolescents may identify those in greatest need for intensive intervention to prevent or delay future disease. One potential screening target is obesity-related inflammation, which contributes to insulin resistance, metabolic syndrome, and CVD. In adults, the inflammatory marker high-sensitivity C-reactive protein (hsCRP) has utility for risk stratification and treatment initiation in individuals of intermediate CVD risk. In adolescents, hsCRP shares many of the associations of hsCRP in adults regarding the degree of insulin resistance, metabolic syndrome, and carotid artery media thickness. However, long-term data linking increased hsCRP levels—and increased insulin or decreased adiponectin—in childhood to adult disease outcomes are lacking at this time. Future efforts continue to be needed to identify childhood clinical and laboratory characteristics that could be used as screening tests to predict adult disease progression. Such tests may have utility in motivating physicians and patients’ families toward lifestyle changes, ultimately improving prevention efforts.

Deficits in weight gain and linear growth are seen frequently among children in areas where malnutrition and recurrent infections are common. Although both inflammation and malnutrition can result in growth hormone (GH) resistance, the interrelationships of infection, inflammation, and growth deficits in developing areas remain unclear. The aim of this study was to evaluate relationships between low levels of systemic inflammation, growth factors, and anthropometry in a case–control cohort of underweight and normal weight children in northern Brazil. We evaluated data from 147 children ages 6 to 24 mo evaluated in the MAL-ED (Interactions of Malnutrition and Enteric Disease) case–control study following recruitment from a nutrition clinic for impoverished families in Fortaleza, Brazil. We used nonparametric tests and linear regression to evaluate relationships between current symptoms of infections (assessed by questionnaire), systemic inflammation (assessed by high-sensitivity C-reactive protein [hsCRP]), the GH insulin-like growth factor-1 (IGF-1) axis, and measures of anthropometry. All models were adjusted for age and sex. Children with recent symptoms of diarrhea, cough, and fever (compared with those without symptoms) had higher hsCRP levels; those with recent diarrhea and fever also had lower IGF-1 and higher GH levels. Stool myeloperoxidase was positively associated with serum hsCRP. hsCRP was in turn positively associated with GH and negatively associated with IGF-1 and IGF-binding protein-3 (IGFBP-3), suggesting a state of GH resistance. After adjustment for hsCRP, IGF-1 and IGFBP-3 were positively and GH was negatively associated with Z scores for height and weight. Infection and inflammation were linked to evidence of GH resistance, whereas levels of GH, IGF-1, and IGFBP-3 were associated with growth indices independent of hsCRP. These data implicate complex interrelationships between infection, nutritional status, GH axis, and linear growth in children from a developing area. •Among children in this developing area, symptoms of illness correlated with high-sensitivity C-reactive protein (hsCRP).•hsCRP correlated positively with growth hormone (GH) and negatively with insulin-like growth factor (IGF)-1 and IGF-binding protein-3 (IGFBP-3).•IGF-1 and IGFBP-3 correlated positively with height.•These data are consistent with a model of inflammation-induced GH resistance.

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.

The metabolic syndrome (MetS) is marked by abnormalities in central obesity, high blood pressure, high triglycerides, low high-density lipoprotein-cholesterol, and high fasting glucose and appears to be produced by underlying processes of inflammation, oxidative stress, and adipocyte dysfunction. MetS has traditionally been classified based on dichotomous criteria that deny that MetS-related risk likely exists as a spectrum. Continuous MetS scores provide a way to track MetS-related risk over time. We generated MetS severity scores that are sex- and race/ethnicity-specific, acknowledging that the way MetS is manifested may be different by sex and racial/ethnic subgroup. These scores are correlated with long-term risk for type 2 diabetes mellitus and cardiovascular disease. Clinical use of scores like these provide a potential opportunity to identify patients at highest risk, motivate patients toward lifestyle change, and follow treatment progress over time.

Given the ongoing strain that the obesity epidemic has placed on public health outcomes, new and effective approaches to weight control are needed. One approach to improving weight and metabolic outcomes is intermittent fasting, which consists of multiple different timing schedules for temporary food avoidance, including alternate-day fasting, other similar full-day fasting patterns, and time-restricted feeding (where the day’s food is consumed over a 6-h period, allowing for 18 h of fasting). These feeding schedules have favorable metabolic effects by intermittently inducing the metabolism of fatty acids to ketones. The regimens overall lead to a decrease in weight and have been linked to improvements in dyslipidemia and blood pressure. While more research is needed on longer-term outcomes and this approach should be avoided in particular health conditions, intermittent fasting should be considered as an option for individuals who have a pattern of unhealthy weight gain using standard eating patterns.

Background The severity of the metabolic syndrome (MetS) is significantly associated with future coronary heart disease (CHD) among individuals without baseline Type 2 diabetes. However, the validity of assessing MetS severity among individuals with diabetes is unknown. Objective To assess for differences in MetS severity by timing of Type 2 diabetes diagnosis and to assess for associations between MetS severity and future CHD among individuals with diabetes. Methods We analyzed data from participants of the Atherosclerosis Risk in Communities study, including 1419 with- and 7241 without diabetes, followed during 4 visits and adjudicated CHD diagnoses over a 20-year period. We used Cox-regression techniques to assess hazard ratios (HR) of CHD based on a sex- and race/ethnicity-specific MetS-severity Z-score (standard MetS score) and a similar MetS-severity score formulated without incorporating glucose as a component of MetS (no-glucose MetS score). Results For both the standard- and no-glucose MetS-severity scores, scores were highest in the baseline-diabetes group, lowest in the never-diabetes group and intermediate in the incident-diabetes groups. Among participants with diabetes, increasing MetS-severity score at baseline was associated with incident CHD, using both the standard MetS score (HR 1.29, 95% confidence interval [CI] 1.21, 1.39) and the no-glucose score (HR 1.42, CI 1.24, 1.62) (both p < 0.001). For the baseline-diabetes group, this relationship remained significant when Visit 2 Hemoglobin-A 1c was included in the model, both for the standard MetS score (HR 1.21, CI 1.09, 1.34; p < 0.001) and the no-glucose score (HR 1.25, CI 1.04, 1.51; p = 0.02). Conclusions MetS severity appears to provide an estimate of metabolic disarray in the setting of diabetes and is predictive of future CHD events beyond HbA1c. Identifying MetS severity among individuals with diabetes may help in identifying those at higher risk, who could then receive further preventative treatment.

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 4 th quartile of MetS-severity (compared to the 1 st ) 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.

The ongoing obesity epidemic in children and adolescents has greatly increased the prevalence of related comorbidities. Prediabetes is defined based on levels of fasting glucose, oral glucose tolerance tests or hemoglobin A1c, that are intermediate between normal levels and thresholds that define type 2 diabetes mellitus (T2DM). As such, prediabetes represents a sign of early pathophysiology preceding T2DM development. Recent analyses of data from US adolescents estimate prediabetes to be present in 4-23% of adolescents, depending on criteria used, with other studies finding an 8% risk of progression from prediabetes to T2DM over a 3-year period. These data support the importance of intervention to avoid long-term sequelae, focusing on reducing degree of obesity and insulin resistance. Lifestyle modification, with increases in physical activity and dietary improvements, remains the first-line approach. Other interventions are based on additional long-term risks and range from metformin treatment for more moderate cases of prediabetes to bariatric surgery for adolescents with severe obesity and comorbidities. As data accumulate regarding sequelae of T2DM in adolescents, there remains a critical need for prevention of obesity and T2DM throughout childhood, and prediabetes should be a trigger for improving this risk profle. Keywords: prediabetes, pediatrics, obesity, type 2 diabetes mellitus, insulin resistance Plain Language Summary Prediabetes represents blood sugar elevations that are above normal but not yet at thresholds that define type 2 diabetes. Prediabetes can be a precursor to later type 2 diabetes and represents an opportunity to improve lifestyle habits (and sometimes treat with medicines) to avoid ever getting type 2 diabetes.

Objective Artificial pancreas (AP) systems have been shown to improve glycemic control throughout the day and night in adults, adolescents, and children. However, AP testing remains limited during intense and prolonged exercise in adolescents and children. We present the performance of the Tandem Control‐IQ AP system in adolescents and children during a winter ski camp study, where high altitude, low temperature, prolonged intense activity, and stress challenged glycemic control. Methods In a randomized controlled trial, 24 adolescents (ages 13‐18 years) and 24 school‐aged children (6‐12 years) with Type 1 diabetes (T1D) participated in a 48 hours ski camp (∼5 hours skiing/day) at three sites: Wintergreen, VA; Kirkwood, and Breckenridge, CO. Study participants were randomized 1:1 at each site. The control group used remote monitored sensor‐augmented pump (RM‐SAP), and the experimental group used the t: slim X2 with Control‐IQ Technology AP system. All subjects were remotely monitored 24 hours per day by study staff. Results The Control‐IQ system improved percent time within range (70‐180 mg/dL) over the entire camp duration: 66.4 ± 16.4 vs 53.9 ± 24.8%; P = .01 in both children and adolescents. The AP system was associated with a significantly lower average glucose based on continuous glucose monitor data: 161 ± 29.9 vs 176.8 ± 36.5 mg/dL; P = .023. There were no differences between groups for hypoglycemia exposure or carbohydrate interventions. There were no adverse events. Conclusions The use of the Control‐IQ AP improved glycemic control and safely reduced exposure to hyperglycemia relative to RM‐SAP in pediatric patients with T1D during prolonged intensive winter sport activities.