Early infant feeding and adiposity risk: from infancy to adulthood

Introduction: Systematic reviews suggest that a longer duration of breast-feeding is associated with a reduction in the risk of later overweight and obesity. Most studies examining breast-feeding in relation to adiposity have not used longitudinal analysis. In our study, we aimed to examine early infant feeding and adiposity risk in a longitudinal cohort from birth to young adulthood using new as well as published data. Methods: Data from the Western Australian Pregnancy Cohort (Raine) Study in Perth, W.A., Australia, were used to examine associations between breast-feeding and measures of adiposity at 1, 2, 3, 6, 8, 10, 14, 17, and 20 years. Results: Breast-feeding was measured in a number of ways. Longer breast-feeding (in months) was associated with reductions in weight z-scores between birth and 1 year (β = -0.027; p \u3c 0.001) in the adjusted analysis. At 3 years, breast-feeding for \u3c4 months increased the odds of infants experiencing early rapid growth (OR 2.05; 95% CI 1.43-2.94; p \u3c 0.001). From 1 to 8 years, children breast-fed for ≤4 months compared to ≥12 months had a significantly greater probability of exceeding the 95th percentile of weight. The age at which breast-feeding was stopped and a milk other than breast milk was introduced (introduction of formula milk) played a significant role in the trajectory of the BMI from birth to 14 years; the 4-month cutoff point was consistently associated with a higher BMI trajectory. Introduction of a milk other than breast milk before 6 months compared to at 6 months or later was a risk factor for being overweight or obese at 20 years of age (OR 1.47; 95% CI 1.12-1.93; p = 0.005). Discussion: Breast-feeding until 6 months of age and beyond should be encouraged and is recommended for protection against increased adiposity in childhood, adolescence, and young adulthood. Adverse long-term effects of early growth acceleration are fundamental in later overweight and obesity. Formula feeding stimulates a higher postnatal growth velocity, whereas breast-feeding promotes slower growth and a reduced likelihood of overweight and obesity. Biological mechanisms underlying the protective effect of breast-feeding against obesity are based on the unique composition and metabolic and physiological responses to human milk

A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly

Copyright © 2003 Massachusetts Medical Society. All rights reserved.Background Treatment of hypertension with diuretics, beta-blockers, or both leads to improved outcomes. It has been postulated that agents that inhibit the renin–angiotensin system confer benefit beyond the reduction of blood pressure alone. We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting–enzyme (ACE) inhibitors with the outcomes in those treated with diuretic agents. Methods We conducted a prospective, randomized, open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practices. Subjects were followed for a median of 4.1 years, and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models. Results At base line, the treatment groups were well matched in terms of age, sex, and blood pressure. By the end of the study, blood pressure had decreased to a similar extent in both groups (a decrease of 26/12 mm Hg). There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group (56.1 per 1000 patient-years) and 736 cardiovascular events or deaths from any cause in the diuretic group (59.8 per 1000 patient-years; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [95 percent confidence interval, 0.79 to 1.00]; P=0.05). Among male subjects, the hazard ratio was 0.83 (95 percent confidence interval, 0.71 to 0.97; P=0.02); among female subjects, the hazard ratio was 1.00 (95 percent confidence interval, 0.83 to 1.21; P=0.98); the P value for the interaction between sex and treatment-group assignment was 0.15. The rates of nonfatal cardiovascular events and myocardial infarctions decreased with ACE-inhibitor treatment, whereas a similar number of strokes occurred in each group (although there were more fatal strokes in the ACE-inhibitor group). Conclusions Initiation of antihypertensive treatment involving ACE inhibitors in older subjects, particularly men, appears to lead to better outcomes than treatment with diuretic agents, despite similar reductions of blood pressure.Lindon M.H. Wing, Christopher M. Reid, Philip Ryan, Lawrence J. Beilin, Mark A. Brown, Garry L.R. Jennings, Colin I. Johnston, John J. McNeil, Graham J. Macdonald, John E. Marley, Trefor O. Morgan, and Malcolm J. West, for the Second Australian National Blood Pressure Study Grou

Dual energy X-ray absorptiometry compared with anthropometry in relation to cardio-metabolic risk factors in a young adult population: Is the ‘Gold Standard’ tarnished?

Background and Aims: Assessment of adiposity using dual energy x-ray absorptiometry (DXA) has been considered more advantageous in comparison to anthropometryfor predicting cardio-metabolic risk in the older population, by virtue of its ability to distinguish total and regional fat. Nonetheless, there is increasing uncertainty regarding the relative superiority of DXA and little comparative data exist in young adults. This study aimed to identify which measure of adiposity determined by either DXA or anthropometry is optimal within a range of cardio-metabolic risk factors in young adults. Methods and Results: 1138 adults aged 20 years were assessed by DXA and standard anthropometry from the Western Australian Pregnancy Cohort (Raine) Study. Cross-sectional linear regression analyses were performed. Waist to height ratio was superior to any DXA measure with HDL-C. BMI was the superior model in relation to blood pressure than any DXA measure. Midriff fat mass (DXA) and waist circumference were comparable in relation to glucose. For all the other cardio-metabolic variables, anthropometricand DXA measures were comparable. DXA midriff fat mass compared with BMI or waist hip ratio was the superior measure for triglycerides, insulin and HOMA-IR. Conclusion: Although midriff fat mass (measured by DXA) was the superior measure with insulin sensitivity and triglycerides, the anthropometricmeasures were better or equal with various DXA measures for majority of the cardio-metabolic risk factors. Our findings suggest, clinical anthropometry is generally as useful as DXA in the evaluation of the individual cardio-metabolic risk factors in young adults

Fat mass and obesity-associated obesity-risk genotype is associated with lower foetal growth: An effect that is reversed in the offspring of smoking mothers

Fat mass and obesity-associated (FTO) gene variants are associated with childhood and adult obesity; however, the influence of FTO polymorphisms on foetal growth is unknown. Associations between the FTO variant rs9939609 and the foetal growth trajectories, maternal pregnancy weight gain, anthropometric measures at birth and body mass index (BMI) at age 14 years were assessed in 1079 singleton-birth Australian Caucasians. Analyses were repeated in 3512 singleton-birth Dutch Caucasians. The rs9939609 obesity-risk AA genotype was associated with symmetrical intrauterine growth restriction; an effect reversed in mothers who smoked during pregnancy. The effect increased over time and was modified by maternal smoking for head circumference (P = 0.007), abdominal circumference (P = 0.007), femur length (P = 0.02) and estimated foetal weight (P = 0.001). The modification of the association between the AA genotype and birth anthropometrics by maternal smoking was consistent across birth weight (P = 0.01) and birth length (P = 0.04) and neonatal day 2 anthropometry. Consistent associations were replicated in the Generation R cohort. Maternal pregnancy weight gain matched the pattern of birth weight and was independent of placental weight. In adolescents, the AA genotype was associated with increased BMI-adjusted-for-age in males (P = 0.00009), but no effect was detected in females. A variant in the FTO gene influences foetal growth trajectories in the third trimester, early postnatal growth and adiposity in adolescence. Maternal smoking during pregnancy reversed the direction of association of rs9939609 on foetal growth, which was probably mediated by maternal energy intake. The detection of genetic variants associated with foetal growth has the potential to identify novel molecular mechanisms underlying growth and targeted early life intervention. Copyrigh

Features of the metabolic syndrome in late adolescence are associated with impaired testicular function at 20 years of age

STUDY QUESTION: Are early signs of metabolic disorder in late adolescence associated with features of impaired testicular function many years before the majority seek parenthood? SUMMARY ANSWER: Adolescents with features of metabolic disorder at 17 years, or insulin resistance (IR) at 20 years of age, show impaired testicular function and altered hormone levels compared to those without metabolic disorder. WHAT IS KNOWN ALREADY: Controversial evidence suggests a recent decline in sperm production potentially linked to environmental influences, but its cause remains unclear. Concomitant increases in obesity and diabetes suggest that lifestyle factors may contribute to this decline in testicular function. Although obesity has been associated with adverse testicular function in some studies, it remains unclear whether poor testicular function merely reflects, or causes, poor metabolic health. If metabolic disorder were present in adolescence, prior to the onset of obesity, this may suggest that metabolic disorder maybe a precursor of impaired testicular function. STUDY DESIGN, SIZE, DURATION: The Western Australian Pregnancy Cohort (Raine) Study is a longitudinal study of children born in 1989-1991 who have undergone detailed physical assessments since birth (1454 male infants born). At 17 years of age, 490 boys underwent a hepatic ultrasound examination, serum cytokine assessment (n = 520) and a metabolic assessment (n = 544). A further metabolic assessment was performed at 20 years (n = 608). Testicular assessment was performed at 20 years; 609 had reproductive hormones measured, 404 underwent a testicular ultrasound and 365 produced a semen sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testicular volume was estimated by ultrasonography, and semen analysis was performed according to World Health Organization guidelines. Concentrations of LH, FSH and inhibin B (inhB) in serum were measured by immunoassay and total testosterone by liquid chromatography-mass spectrometry.At 17 years of age, a liver ultrasound examination was performed to determine the presence of non-alcoholic fatty liver disease (NAFLD), and serum analysed for the cytokines interleukin-18 and soluble tumour necrosis factor receptor 1 and 2 (sTNFR1, sTNFR2).At 17 and 20 years of age, fasting blood samples were analysed for serum liver enzymes, insulin, glucose, triglycerides (TG), total cholesterol, high density lipoprotein and low density lipoprotein cholesterol, high sensitivity C-reactive protein and uric acid. The homoeostatic model assessment (HOMA) was calculated and approximated IR was defined by a HOMA \u3e4. Anthropometric data was collected and dual energy X-ray absorptiometry measurement performed for lean and total fat mass. As at this young age the prevalence of metabolic syndrome was expected to be low, a two-step cluster analysis was used using waist circumference, TGs, insulin, and systolic blood pressure to derive a distinct high-risk group with features consistent with the metabolic syndrome and increased cardiometabolic risk. MAIN RESULTS AND THE ROLE OF CHANCE: Men at age 17 years with increased cardiometabolic risk had lower concentrations of serum testosterone (medians: 4.0 versus 4.9 ng/mL) and inhB (193.2 versus 221.9 pg/mL) (P \u3c 0.001 for both) compared to those within the low risk metabolic cluster. Men with ultrasound evidence of NAFLD (n = 45, 9.8%) had reduced total sperm output (medians: 68.0 versus 126.00 million, P = 0.044), testosterone (4.0 versus 4.7 ng/mL, P = 0.005) and inhB (209.1 versus 218.4 pg/mL, P = 0.032) compared to men without NAFLD.Men with higher concentrations of sTNFR1 at 17 years of age had a lower sperm output and serum concentration of inhB, with an increase in LH and FSH (all P \u3c 0.05 after adjustment for age, BMI, abstinence and a history of cryptorchidism, varicocele, cigarette smoking, alcohol and drug use), compared to those without an elevated sTNFR1. Multivariable regression analysis, adjusting for confounders, demonstrated that men in the high-risk metabolic cluster at 20 years had a lower serum testosterone and inhB (P = 0.003 and P = 0.001, respectively). A HOMA-IR \u3e 4 was associated with a lower serum testosterone (P = LIMITATIONS, REASONS FOR CAUTION: This study is limited by the sample size and multiple comparisons, and causality cannot be proven from an observational study. Due to a 3-year interval between some metabolic assessments and assessment of testicular function, we cannot exclude the introduction of a bias into the study, as some of the participants and their testicular function will not have been fully mature at the 17-year assessment. WIDER IMPLICATIONS OF THE FINDINGS: Irrespective of a proven causation, our study findings are important in that a significant minority of the men, prior to seeking parenthood, presented co-existent features of metabolic disorder and signs of testicular impairment. Of particular note is that the presence of NAFLD at 17 years of age, although only present in a minority of men, was associated with an almost 50% reduction in sperm output at 20 years of age, and that the presence of IR at 20 years was associated with a 20% reduction in testicular volume. STUDY FUNDING/ COMPETING INTEREST(S): This study was supported by Australian NHMRC (Grant Numbers 634457, 35351417 and 403981) and received support from the Raine Medical Research Foundation, The Telethon Kids Institute, University of Western Australia, Women and Infants Research Foundation, Curtin University and Edith Cowan University. D.A.D., J.E.D., N.M., L.A.A., R.-C.H., T.A.M., J.K.O., L.J.B. have nothing to declare. R.J.H. is Medical Director of Fertility Specialists of Western Australia, has equity interests in Western IVF, and has received grant support from MSD, Merck-Serono and Ferring Pharmaceuticals. RMcL has equity interests in the Monash IVF Group. R.J.N. has equity interests in FertilitySA, and has received grant support from Merck Serono and Ferring Pharmaceuticals. D.J.H. has received institutional grant funding (but no personal income) for investigator-initiated testosterone pharmacology studies from Lawley and Besins Healthcare and has provided expert testimony to anti-doping tribunals and for testosterone litigation.This abstract was awarded the Fertility Society of Australia clinical exchange award for the oral presentation at ESHRE, Barcelona, in 2018

Instability and `Sausage-String' Appearance in Blood Vessels during High Blood Pressure

A new Rayleigh-type instability is proposed to explain the `sausage-string' pattern of alternating constrictions and dilatations formed in blood vessels under influence of a vasoconstricting agent. Our theory involves the nonlinear elasticity characteristics of the vessel wall, and provides predictions for the conditions under which the cylindrical form of a blood vessel becomes unstable.Comment: 4 pages, 4 figures submitted to Physical Review Letter

Comparison of the cardiometabolic profiles of adolescents conceived through ART with those of a non-ART cohort

STUDY QUESTION: Is the cardiometabolic health of adolescents conceived through ART worse than that of their counterparts conceived without ART? SUMMARY ANSWER: The majority of cardiometabolic and vascular health parameters of adolescents conceived through ART are similar or more favourable, than those of their counterparts of similar age and conceived without ART. WHAT IS KNOWN ALREADY: It has been proposed that the cardiometabolic health of offspring conceived with ART may be unfavourable compared to that of their counterparts conceived without ART. The literature pertaining to cardiometabolic health of offspring conceived after ART is contradictory, but generally suggests unfavourable cardiometabolic health parameters, such as an increase in blood pressure (BP), vascular dysfunction and adiposity, as well as unfavourable glucose and lipid profiles. With over 8 million children and adults born through ART worldwide, it is important to investigate whether these early signs of adverse cardiometabolic differences persist into adolescence and beyond. STUDY DESIGN, SIZE, DURATION: The Growing Up Healthy Study (GUHS) is a prospective cohort study that recruited 303 adolescents and young adults conceived after ART (aged 13-21 years) and born between 1991 and 2001 in Western Australia. Their health parameters, including cardiometabolic factors, were assessed and compared with counterparts from the Raine Study Generation 2 (Gen2). The 2868 Gen2 participants were born 1989-1992 and are representative of the Western Australian adolescent population. At ∼17 years of age (2013-2017), 163 GUHS participants replicated assessments previously completed by Gen2 at a similar age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cardiometabolic parameters were compared between a total of 163 GUHS and 1457 Gen2 adolescents. Separate male (GUHS n = 81, Gen2 n = 735) and female (GUHS n = 82, Gen2 n = 722) analyses were conducted. Assessments consisted of a detailed questionnaire including health, lifestyle and demographic parameters, anthropometric assessments (height, weight, BMI, waist circumference and skinfold thickness), fasting serum biochemistry, arterial stiffness and BP (assessed using applanation tonometry). Abdominal ultrasonography was used to assess the presence and severity of hepatic steatosis, and thickness of abdominal fat compartments. Non-alcoholic fatty liver disease (NAFLD) was diagnosed if there was sonographic fatty liver in the absence of significant alcohol consumption. Chi2, Fisher\u27s exact and Mann-Whitney U tests, performed in SPSS V25, examined cohort differences and generalized estimating equations adjusted for the following covariates: singleton vs non-singleton pregnancy, birthweight (z-score), gestational age, BMI, smoking, alcohol consumption in the past 6 months and parent cardiovascular status. Arterial stiffness measures and waist circumference were additionally adjusted for height, and female analyses were additionally adjusted for use of oral contraceptives in the preceding 6 months. MAIN RESULTS AND THE ROLE OF CHANCE: In adjusted analyses, GUHS females had a lower BMI (22.1 vs 23.3 kg/m2, P = 0.014), and thinner skinfolds (triceps, subscapular, mid-abdominal; 16.9 vs 18.7 mm, P = 0.021, 13.4 vs 15.0 mm, P = 0.027, 19.7 vs 23.2 mm, P \u3c 0.001, respectively), whereas males were not significantly different. Waist circumference was lower in GUHS adolescents (males: 78.1 vs 81.3 cm, P = 0.008, females: 76.7 vs 83.3 cm, P = 0.007). There were no significant differences between the two groups in glucose, insulin, homeostatic model assessment for insulin resistance, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), alanine aminotransferase and high-sensitivity C-reactive protein in both sexes. In females, serum triglycerides were lower in GUHS adolescents (1.0 vs 1.2 mmol/l, P = 0.029). GUHS males had higher serum HDL-C (1.1 vs 1.0 mmol/l, P = 0.004) and a lower TC/HDL-C ratio (3.2 vs 3.6, P = 0.036). There were no significant differences in the prevalence of NAFLD or steatosis severity scores between the cohorts in males and females. GUHS females had less subcutaneous adipose tissue (9.4 vs 17.9 mm, P \u3c 0.001), whereas GUHS males had greater visceral adipose thickness (44.7 vs 36.3 mm, P \u3c 0.001). There was no significant difference in pre-peritoneal adipose thickness. Pulse wave velocity was lower in GUHS males (5.8 vs 6.3 m/s, P \u3c 0.001) and heart rate corrected augmentation index was lower in GUHS females (-8.4 vs -2.7%, P = 0.048). There were no significant differences in BP or heart rate in males or females between the two groups. LIMITATIONS, REASONS FOR CAUTION: Despite the substantial study size and the unique study design of the ART cohort, we were unable to differentiate between different types of ART, due to the low number of ICSI cycles (e.g. IVF vs ICSI), draw definite conclusions, or relate the outcomes to the cause of infertility. Considering the differences in time points when both cohorts were studied, external factors could have changed, which could not be accounted for. Given the observational nature of this study, causation cannot be proven. WIDER IMPLICATIONS OF THE FINDINGS: Contrary to our hypothesis and previous findings focussing mainly on childhood, this study reports mostly similar or favourable cardiometabolic markers in adolescents conceived with ART compared to those conceived without ART. The greater visceral adipose thickness, particularly present in males, requires further investigation. While these findings are generally reassuring, future well-designed and appropriately powered studies are required to definitively address the issue of cardiometabolic health in ART adults

Dynamic response of HTS composite tapes to pulsed currents

Dynamic voltage-current characteristics of an HTS Ag/BiSCCO composite tape are studied both experimentally and theoretically. The tape is subjected by pulsed currents with different shapes and magnitude and voltage traces are measured using the four-point method with different location of potential taps on the sample surface. Clockwise and anticlockwise hysteresis loops are obtained for the same sample depending on location of the potential taps. The dynamic characteristics deviate substantially from the DC characteristic, especially in the range of low voltages where a criterion for the critical current value is usually chosen (1-10 mkV/cm). The critical current determined from dynamic characteristics and its change with the pulse magnitude depend on location of the potential taps and on the curve branch chosen for the critical current determination (ascending or descending). The theoretical analysis is based on a model of the magnetic flux diffusion into a composite tape for a superconductor described by the flux creep characteristic. Numerical simulation based on this model gives the results in good agreement with the experimental ones and explains the observed peculiarities of the dynamic characteristics of HTS composite tapes. The difference between the magnetic diffusion into a tape and a slab is discussed.Comment: 18 pages, 13 figure