Early Life Determinants of Vascular Structure in Fetuses, Infants, Children, and Adolescents: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the association between early life exposures during the first 1000 days (conception to age 24 months) and aortic intima-media thickness (aIMT), an early indicator of cardiovascular disease (CVD) risk, in youths. STUDY DESIGN: The MEDLINE, Embase, Scopus, CINAHL, and Allied and Complementary Medicine databases were searched from inception to July 2021. Eligibility criteria included observational controlled studies in youths aged <20 years with risk factors/exposures during the first 1000 days and aIMT measurements (unadjusted mean ± SD). Outcome data were pooled using a random-effects meta-analysis. Meta-regression was used to investigate confounders. RESULTS: A total of 8657 articles were identified, of which 34 were included in our meta-analysis. The age of participants ranged from 22.9 weeks gestation in utero to 10.9 years. In the meta-analysis (n = 1220 cases, n = 1997 controls), the following factors were associated with greater aIMT: small for gestational age (SGA) status (14 studies, mean difference, 0.082 mm; 95% CI, 0.051-0.112; P < .001; I2 = 97%), intrauterine growth restriction (6 studies; mean difference, 0.198 mm, 95% CI, 0.088-0.309; P < .001; I2 = 97%), preeclampsia (2 studies; mean difference, 0.038 mm; 95% CI, 0.024-0.051; P < .001; I2 = 38%), and large for gestational age (LGA) status (3 studies; mean difference, 0.089 mm; 95% CI, 0.043-0.0136; P < .001; I2 = 93%). In meta-regression, older age (P < .001), higher prevalence of maternal smoking (P = .04), and SGA (P < .001) were associated with greater difference in aIMT in preterm participants compared with controls. Limitations included the high heterogeneity present in most meta-analyses and the scope of our meta-regression. CONCLUSIONS: Adverse early life exposures are associated with greater aIMT in youths, consistent with an increased risk for CVD later in life. Further research is needed to determine whether intervention and preventive strategies deliver clinical benefits to improve future cardiovascular health.

Higher frequency of cardiovascular autonomic neuropathy in youth with type 2 compared to type 1 diabetes: Role of cardiometabolic risk factors.

OBJECTIVE: Cardiovascular autonomic neuropathy (CAN) is an overlooked but common and serious diabetes complication. We examined CAN in youth with diabetes and associations with cardiovascular risk factors. RESEARCH DESIGN AND METHODS: This was a prospective cohort of youth aged <20 years with type 2 or type 1 diabetes (n = 66/1153, median age 15.4/16.5 years, duration 1.7/8.0 years), assessed between 2009 and 2020. CAN was defined as ≥2 abnormal heart rate variability measures across time, geometric, and frequency domains. Obesity was defined as BMI ≥ 95th percentile and severe obesity as ≥120% of 95th percentile. Multivariable generalized estimating equations (GEE) were used to examine putative risk factors for CAN, including diabetes type, obesity, and HbA1c . RESULTS: At most recent assessment, youth with type 2 versus type 1 diabetes had median: HbA1 c 7.1% (54 mmol/mol) versus 8.7% (72 mmol/mol) and BMI SDS (2.0 vs. 0.7); frequency of CAN (47% vs. 27%), peripheral nerve abnormality (47% vs. 25%), hypertension (29% vs. 12%), albuminuria (21% vs. 3%), and severe obesity (35% vs. 2%). In multivariable GEE, CAN was associated with type 2 diabetes: Odds Ratio 2.53, 95% CI 1.46, 4.38, p = 0.001, higher BMI SDS: 1.49, 95% CI 1.29, 1.73, p < 0.0001, and obesity: 2.09, 95% CI 1.57, 2.78, p < 0.0001. CONCLUSIONS: Youth with type 2 diabetes have a higher frequency of CAN, peripheral nerve abnormality, hypertension, albuminuria and severe obesity despite shorter diabetes duration and younger age. Our findings highlight the importance of targeting modifiable risk factors to prevent cardiovascular disease in youth with diabetes.

Early life determinants of arterial stiffness in neonates, infants, children and adolescents: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Certain exposures and risk factors during the first 1,000 days of life are known to influence future cardiovascular disease (CVD) risk. Pulse wave velocity (PWV) is a measure of arterial stiffness and a recognised surrogate marker of CVD. We performed a systematic review and meta-analyses to investigate whether early life exposures were associated with increased PWV compared with controls in youth. METHODS: Databases AMED, MEDLINE, EMBASE, CINAHL and Scopus were searched from inception until February 2022. ELIGIBILITY CRITERIA: observational controlled studies in youth aged <20 years with risk factors/exposure during the first 1,000 days and PWV measurement. This review is registered with PROSPERO (CRD42019137559). Outcome data were pooled using random-effects meta-analysis. Meta-regression was used to investigate potential confounders. RESULTS: We identified 24 eligible studies. Age of participants ranged from 1-day to 19-years at time of PWV assessment. Exposures included pre-term birth, small for gestational age (SGA), maternal diabetes and assisted reproductive technologies, none of which were significantly associated with PWV in meta-analysis. Sub-group analysis by age demonstrated increased PWV in childhood and adolescence in those exposed to maternal diabetes or born SGA. In meta-regression of pre-term studies, higher prevalence of SGA was associated with increased PWV compared with controls (p = 0.034, R2 = 1). CONCLUSIONS: We found limited evidence that youth exposed to maternal diabetes or born SGA have increased PWV, consistent with increased future CVD risk. These changes in PWV appear to manifest in later childhood and adolescence. Further research is required to better understand the observed relationships.

Aortic intima media thickness in children and adolescents with type 1 diabetes: A systematic review.

AIMS: Greater aortic intima media thickness (aIMT), a marker of subclinical atherosclerosis, can identify individuals at risk of CVD. This systematic review with meta-analysis compared aIMT in youth with type 1 diabetes and healthy controls. METHODS: A systematic search of published literature (to July 2021) was undertaken using electronic databases MEDLINE, EMBASE, Scopus, CINAHL and AMED. Eligible studies reported aIMT in participants aged <20 years with type 1 diabetes and healthy controls. Meta-analysis was used to combine outcome data, presented as forest plots. Moderator analysis and metaregression were conducted to identify study and participant characteristics associated with aIMT. Publication bias was assessed by funnel plot inspection. RESULTS: Meta-analysis of nine studies (n = 1030 with type 1 diabetes and n = 498 healthy control participants) indicated, with high heterogeneity (I2 98%), that youth with type 1 diabetes have higher aIMT compared with healthy controls (mean difference [95% CIs]: 0.11 [0.04, 0.18] mm, P = 0.003). Factors associated with greater aIMT in type 1 diabetes compared to controls included: use of a phased array probe versus linear array probe; longer diabetes duration; higher insulin dose; higher BMI z score and waist circumference; higher LDL cholesterol; higher triglycerides; and higher diastolic blood pressure. CONCLUSIONS: Type 1 diabetes in youth is associated with higher aIMT compared with healthy control individuals. Longer duration of diabetes and major CVD risk factors were also associated with higher aIMT. Together, these findings provide a strong rationale for targeting modifiable risk factors in CVD prevention. Registered in PROSPERO on 8 August 2019 (CRD42019137559).

Intrauterine exposure to preeclampsia does not impair vascular health in children.

Background and objectives: Preeclampsia is a serious multisystem blood pressure disorder during pregnancy that is associated with increased long-term risk of cardiovascular disease to the mother and offspring. We investigated the vascular health of children exposed to intrauterine preeclampsia. Materials and methods: This was a cross-sectional study of offspring in a prospective cohort of women with complications during pregnancy. Children aged between 2 and 5 years [median age 4.7 (2.8, 5.1) years] exposed to intrauterine preeclampsia (n = 26) or normotensive controls (n = 34), were recruited between July 2020 and April 2021. Vascular health was assessed by measuring aortic intima-media thickness and pulse wave velocity. Univariate generalized linear regression models were used to explore associations between vascular measurements and explanatory variables. Results: Children exposed to preeclampsia had a lower body mass index at assessment (15.5 vs. 16.2 kg/m2, p = 0.04), birth weight (2.90 vs. 3.34 kg, p = 0.004), gestational age at birth (37.5 vs. 39.4 weeks, p < 0.001) and higher frequency of preterm birth (27% vs. 6%, p = 0.02). There were no differences in vascular health between children exposed to preeclampsia vs. controls (mean aortic intima-media thickness 0.575 mm vs. 0.563 mm, p = 0.51, pulse wave velocity 4.09 vs. 4.18 m/s, p = 0.54) and there were no significant associations in univariate analyses. Conclusions: There were no major adverse differences in vascular health which contrasts with existing studies. This suggests exposure to intrauterine preeclampsia may result in a less severe cardiovascular phenotype in young children. While reassuring, longitudinal studies are required to determine if and when exposure to intrauterine preeclampsia affects vascular health in children.

Revisiting Poststroke Upper Limb Stratification: Resilience in a Larger Cohort.

BACKGROUND: Upper limb (UL) impairment in stroke survivors is both multifactorial and heterogeneous. Stratification of motor function helps identify the most sensitive and appropriate assessments, which in turn aids the design of effective and individualized rehabilitation strategies. We previously developed a stratification method combining the Grooved Pegboard Test (GPT) and Box and Block Test (BBT) to stratify poststroke UL motor function. OBJECTIVE: To investigate the resilience of the stratification method in a larger cohort and establish its appropriateness for clinical practice by investigating limitations of the GPT completion time. METHODS: Post hoc analysis of motor function for 96 community-dwelling participants with stroke (n = 68 male, 28 female, age 60.8 ± 14 years, 24.4 ± 36.6 months poststroke) was performed using the Wolf Motor Function Test (WMFT), Fugl-Meyer Assessment (F-M), BBT, and GPT. Hypothesis-free and hypothesis-based hierarchical cluster analyses were conducted to determine the resilience of the stratification method. RESULTS: The hypothesis-based analysis identified the same functional groupings as the hypothesis-free analysis: low (n = 32), moderate (n = 26), and high motor function (n = 38), with 3 exceptions. Thirty-three of the 38 participants with fine manual dexterity completed the GPT in ≤5 minutes. The remaining 5 participants took 6 to 25 minutes to place all 25 pegs but used alternative movement strategies to complete the test. The GPT time restriction changed the functional profile of the moderate and high motor function groups leading to more misclassifications. CONCLUSION: The stratification method unambiguously classifies participants by UL motor function. While the inclusion of a 5-minute cutoff time for the GPT is preferred for clinical practice, it is not recommended for stratification purposes.

Current Perspectives on the Role of Very-Low-Energy Diets in the Treatment of Obesity and Type 2 Diabetes in Youth.

In both developed and developing countries, pediatric obesity and type 2 diabetes are an increasing public health concern: globally 5.6% of girls and 7.8% of boys aged ≥5 years have obesity. The incidence of type 2 diabetes has increased in youth in recent decades and disproportionately affects those from ethnic/racial minority groups and disadvantaged backgrounds. For the treatment of both conditions, conventional lifestyle intervention is frequently ineffective, access to bariatric surgery is very limited and many young people are unsuitable or unwilling to undergo surgery. A very-low-energy diet (VLED) provides a viable alternative and may be effective for weight reduction and improved glycemic control in youth, based on one systematic review. In particular, in the treatment of type 2 diabetes, a chart review and a pilot study both demonstrated that a VLED can reduce the requirement for medications, including insulin, and lead to the remission of diabetes. However, long-term follow-up and safety data remain limited and therefore a VLED is inconsistently recommended by clinical practice guidelines for the treatment of pediatric obesity and type 2 diabetes. In clinical practice, VLED use in children and adolescents is uniquely challenging due to intolerance of expected side effects, difficulty adhering to the highly restrictive diet and difficulty with behaviour change within the current social context and environment. Ultimately, more research, including larger, longer-term trials with comprehensive safety monitoring are required to strengthen the evidence base. This would inform clinical practice guidelines, which may facilitate more widespread utilization of VLED programs in the management of obesity and type 2 diabetes in youth.

A Low-Carbohydrate Ketogenic Diet Reduces Body Mass Without Compromising Performance in Powerlifting and Olympic Weightlifting Athletes.

Greene, DA, Varley, BJ, Hartwig, TB, Chapman, P, and Rigney, M. A low-carbohydrate ketogenic diet reduces body mass without compromising performance in powerlifting and Olympic weightlifting athletes. J Strength Cond Res 32(12): 3382-3391, 2018-Weight class athletes use weight-making strategies to compete in specific weight categories with an optimum power-to-weight ratio. There is evidence that low carbohydrate diets might offer specific advantages for weight reduction without the negative impact on strength and power previously hypothesized to accompany carbohydrate restriction. Therefore, the purpose of this study was to determine whether a low-carbohydrate ketogenic diet (LCKD) could be used as a weight reduction strategy for athletes competing in the weight class sports of powerlifting and Olympic weightlifting. Fourteen intermediate to elite competitive lifting athletes (age 34 ± 10.5, n = 5 female) consumed an ad libitum usual diet (UD) (>250 g daily intake of carbohydrates) and an ad libitum LCKD (≤50 g or ≤10% daily intake of carbohydrates) in random order, each for 3 months in a crossover design. Lifting performance, body composition, resting metabolic rate, blood glucose, and blood electrolytes were measured at baseline, 3 months, and 6 months. The LCKD phase resulted in significantly lower body mass (-3.26 kg, p = 0.038) and lean mass (-2.26 kg, p = 0.016) compared with the UD phase. Lean mass losses were not reflected in lifting performances that were not different between dietary phases. No other differences in primary or secondary outcome measures were found between dietary phases. Weight class athletes consuming an ad libitum LCKD decreased body mass and achieved lifting performances that were comparable with their UD. Coaches and athletes should consider using an LCKD to achieve targeted weight reduction goals for weight class sports.