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Objective: To determine whether silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) or laparoscopic sleeve gastrectomy (LSG) produces superior diabetes remission at 5 years.Research Design and Methods: In a single-center, double-blind trial, 114 adults with type 2 diabetes and BMI 35-65 kg/m2 were randomly assigned to SR-LRYGB or LSG (1:1; stratified by age-group, BMI group, ethnicity, diabetes duration, and insulin therapy) using a web-based service. Diabetes and other metabolic medications were adjusted according to a prespecified protocol. The primary outcome was diabetes remission assessed at 5 years, defined by HbA1c <6% (42 mmol/mol) without glucose-lowering medications. Secondary outcomes included changes in weight, cardiometabolic risk factors, quality of life, and adverse events.Results: Diabetes remission after SR-LRYGB versus LSG occurred in 25 (47%) of 53 vs. 18 (33%) of 55 patients (adjusted odds ratios 4.5 [95% CI 1.6, 15.5; P = 0.009] and 4.2 [1.3, 13.4; P = 0.015] in the intention-to-treat analysis). Percent body weight loss was greater after SR-LRYGB than after LSG (absolute difference 10.7%; 95% CI 7.3, 14.0; P < 0.001). Improvements in cardiometabolic risk factors were similar, but HDL cholesterol increased more after SR-LRYGB. Early and late complications were similar in both groups. General health and physical functioning improved after both types of surgery, with greater improvement in physical functioning after SR-LRYGB. People of Māori or Pacific ethnicity (26%) had lower incidence of diabetes remission than those of New Zealand European or other ethnicities (2 of 25 vs. 41 of 83; P < 0.001).Conclusions: SR-LRYGB provided superior diabetes remission and weight loss compared with LSG at 5 years, with similar low risks of complications. [ABSTRACT FROM AUTHOR]

Objective: Levels of fibroblast growth factor 23 (FGF23) have been positively associated with measures of adiposity, cardiovascular disease and mortality. It is unclear whether the relationship of FGF23 with cardiovascular disease and mortality is confounded by obesity. We aimed to determine whether FGF23 concentrations decline following a reduction in adiposity after sleeve gastrectomy (SG). Design: The effect of SG on FGF23 was evaluated in 22 obese adults (59% male) with type 2 diabetes. Fat mass, weight, BMI, plasma intact FGF23, parathyroid hormone (PTH) and leptin were determined at baseline and at 12 months following SG. Results: At baseline, median (IQR) age was 51 (43‐54) years, fat mass 47.8 (41.0‐59.4) kg, BMI 40.9 (36.9‐46.9) kg/m2 and FGF23 66.2 (55.3‐82.9) pg/mL. Significant changes in median BMI (−10.8 kg/m2, 95% CI: −12.9 to −7.2, P < 0.0001), fat mass (−20.0 kg, 95% CI: −26.7 to −12.4, P < 0.0001) and weight (−34.7 kg, 95% CI −40.0 to −23.1, P < 0.0001) were observed after SG. FGF23 (−12.4 pg/mL, 95% CI: −19.5 to 2.0, P = 0.005), PTH (−1.1 pmol/L, 95% CI: −1.7 to 0.2, P = 0.009) and leptin (−1687 pg/mL, 95% CI −4524 to −563, P = 0.01) declined following SG. Change in FGF23 was not significantly associated with change in measures of adiposity, PTH or leptin. Conclusions: FGF23 concentrations decline in the setting of significant weight loss following SG, implying that increased FGF23 concentrations are a downstream consequence of obesity, which may confound its association with cardiometabolic dysfunction. Mediators of the relationship between adiposity and FGF23 require further elucidation. [ABSTRACT FROM AUTHOR]

Inequitable access to bariatric surgery by geographical region has been reported internationally, but comparable data on provision of bariatric surgery have not previously been reported in New Zealand. We examined allocated funding and provision of bariatric surgery amongst different regions in New Zealand in the 2013/14 year, and found that there was large variation in both. This highlights that public funded bariatric surgery needs to take into account population prevalence of morbid obesity to reduce inequities by geographical region. [ABSTRACT FROM AUTHOR]

Background: Fructose consumption has been linked with insulin resistance, obesity and diabetes, which are more prevalent in those of Māori or Pacific ethnicity compared to New Zealand European. Aim: To determine whether the acute effects of fructose consumption on serum glucose, insulin, lipids and C‐reactive protein differs according to body mass index (BMI) and/or ethnicity. Methods: Participants of Māori (n = 25), Pacific (n = 26) or New Zealand European (n = 25) ethnicity consumed a 64 g fructose/16 g glucose solution. Changes in lipids, glucose, insulin and C‐reactive protein were analysed using mixed models for repeated measures. Results: After adjustment for age and gender, those with higher BMI had a higher glucose (P = 0.0064) and insulin (P = 0.0007) response than those with lower BMI. Those of Māori or Pacific ethnicity had similar glucose levels (P = 0.077) to those of New Zealand European ethnicity but higher insulin responses (P = 0.0005), which remained after additional adjustment for BMI (P = 0.001). Reported sugar‐sweetened beverages (SSB) intake was higher among Māori and Pacific than New Zealand European (median 1.0 vs 0.0 SSB/day P = 0.002). Conclusion: Even after adjustment for BMI, those of Māori and Pacific ethnicity have a significantly higher insulin response to fructose than New Zealand Europeans. Higher habitual SSB intake may be a contributing factor. [ABSTRACT FROM AUTHOR]

Dysbiosis is linked to human disease; therefore, gut microbiota modulation strategies provide an attractive means of correcting microbial imbalance to enhance human health. Because diet has amajor influence on the composition, diversity, and metabolic capacity of the gut microbiota, numerous dietary intervention studies have been conducted tomanipulate the gutmicrobiota to improve host outcomes and reduce disease risk. Emerging evidence suggests that interindividual variability in gut microbiota and host responsiveness exists, making it difficult to predict gut microbiota and host response to a given dietary intervention. This may, in turn, have implications on the consistency of results among studies and the perceived success or true efficacy of a dietary intervention in eliciting beneficial changes to the gut microbiota and human health [ABSTRACT FROM AUTHOR]

Children born small for gestational age (SGA) have an increased risk of cardiovascular disease (CVD) and associated risk factors in later life; however, little is known about their dietary intakes. The objective of this study was to assess dietary intakes in SGA and appropriate for gestational age (AGA) at 3.5, 7, and 11 years. The Auckland Birthweight Collaborative Study is a longitudinal case-control study of children born at term ( n = 871). Children were assessed at 3.5 ( n = 550), 7 ( n = 591), and 11 ( n = 620) years of age. Diet was assessed using a 24-hr record-assisted recall. Reported dietary intakes were analyzed and compared with the Australian and New Zealand Nutrient Reference Values. Compared with AGA, median energy intakes were significantly lower in SGA at 3.5 years (4.2 MJ [IQR, 3.0 to 5.8] vs. 5.4 MJ [IQR, 3.9 to 6.5]; p < .0001) but not at 7 and 11 years. Inadequate dietary intakes of micronutrients were more prevalent among SGA at 3.5 years and 11 years of age. A large proportion of SGA and AGA children consumed more than the recommended amounts of saturated fats, sugars, and sodium. There was no association of dietary intake and socio-demographic factors. This study reveals that dietary intake in 3.5-year-old children born SGA is lower in energy and a variety of micronutrients compared with dietary intake in AGA. These intakes may however be appropriate given their BMI z-scores. High intakes of sodium, saturated fat, and sugars are a concern for all children in this cohort. [ABSTRACT FROM AUTHOR]

Monogenic diabetes is frequently mistakenly diagnosed as either type 1 or type 2 diabetes, yet accounts for approximately 1–2% of diabetes. Identifying monogenic forms of diabetes has practical implications for specific therapy, screening of family members and genetic counselling. The most common forms of monogenic diabetes are due to glucokinase (GCK), hepatocyte nuclear factor (HNF)-1A and HNF-4A, HNF-1B, m.3243A>G gene defects. Practical aspects of their recognition, diagnosis and management are outlined, particularly as they relate to pregnancy. This knowledge is important for all physicians managing diabetes in pregnancy, given this is a time when previously unrecognised monogenic diabetes may be uncovered with careful attention to atypical features of diabetes misclassified as type 1, type 2, or gestational diabetes. [ABSTRACT FROM AUTHOR]

Background: Current guidelines for the management of type 2 diabetes and gout recommend that people with these conditions limit their sugar sweetened beverage (SSB) intake. We examined self-reported SSB intake among New Zealand adults with gout or type 2 diabetes, including those on hemodialysis. Method: 1023 adults with gout and 580 adults (including 206 receiving hemodialysis) with type 2 diabetes, participated in this study of between 2009 and 2012. Participants completed an interviewer-administered SSB intake question “how many sugar sweetened drinks (including fruit juice), but not including diet drinks, do you normally drink per day?” SSB consumption was recorded as a circled number 0, 1, 2, 3, 4, 5, or >5, cans or large glasses (300mL) per day. Results: Consuming one or more SSB per day was reported by 64% (622/1023) of subjects with gout, 49% (176/374) with type 2 diabetes without dialysis, and 47% (96/206) with diabetes on dialysis. Consuming four or more SSBs per day was reported by 18% (179/1023), 9% (31/374) and 9% (18/206), respectively. Such high consumers of SSB were characterized after multivariable analysis to be more likely to be male (adjusted odds ratio (OR) 1.8; 95% confidence interval 1.1–2.9), younger in age (40 vs 65 years: 1.6; 1.1–2.3), current smoker (5.2; 2.7–10.1), obese (BMI 41 vs 26kg/m2: 1.4; 1–1.9), and report Māori (1.8; 1.2–2.8) or Pacific (1.6; 1.1–2.5) ancestry, compared to Caucasian. People with gout were more likely to report heavy SSB intake compared to people with diabetes (OR 2.4, 95% CI 1.5–3.9). Heavy SSB consumption reported by people with diabetes was similar if they did or did not require dialysis. Conclusion: A high proportion of patients with gout and type 2 diabetes, including those on haemodialysis, are not responding to health messages to abstain from SSB consumption. [ABSTRACT FROM AUTHOR]

Background There is a substantial genetic component for birthweight variation, and although there are known associations between fetal genotype and birthweight, the role of common epigenetic variation in influencing the risk for small for gestational age (SGA) is unknown. The two imprinting control regions (ICRs) located on chromosome 11p15.5, involved in the overgrowth disorder Beckwith-Wiedemann syndrome (BWS) and the growth restriction disorder Silver-Russell syndrome (SRS), are prime epigenetic candidates for regulating fetal growth. We investigated whether common variation in copy number in the BWS/SRS 11p15 region or altered methylation levels at IGF2/H19 ICR or KCNQ10T1 ICR was associated with SGA. Methods We used a methylation-specific multiplex-ligation-dependent probe amplification assay to analyse copy number variation in the 11p15 region and methylation of IGF2/H19 and KCNQ10T1 ICRs in blood samples from 153 children (including 80 SGA), as well as bisulfite pyrosequencing to measure methylation at IGF2 differentially methylated region (DMR)0 and H19 DMR. Results No copy number variants were detected in the analyzed cohort. Children born SGA had 2.7% lower methylation at the IGF2 DMR0. No methylation differences were detected at the H19 or KCNQ10T1 DMRs. Conclusions We confirm that a small hypomethylation of the IGF2 DMR0 is detected in peripheral blood leucocytes of children born SGA at term. Copy number variation within the 11p15 BWS/SRS region is not an important cause of non-syndromic SGA at term. [ABSTRACT FROM AUTHOR]

Monogenic forms of beta cell diabetes account for approximately 1%-2% of all cases of diabetes, yet remain underdiagnosed. Overlapping clinical features with common forms of diabetes, make diagnosis challenging. A genetic diagnosis of monogenic diabetes in many cases alters therapy, affects prognosis, enables genetic counseling, and has implications for cascade screening of extended family members. We describe those types of monogenic beta cell diabetes which are recognisable by distinct clinical features and have implications for altered management; the cost effectiveness of making a genetic diagnosis in this setting; the use of complementary diagnostic tests to increase the yield among the vast majority of patients who will have commoner types of diabetes which are summarised in a clinical algorithm; and the vital role of cascade genetic testing to enhance case finding. [ABSTRACT FROM AUTHOR]

Identifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin resistance and type 2 diabetes are linked to obesity and driven by excess caloric intake and reduced physical activity. However, key events in the causation of the metabolic syndrome are difficult to disentangle from compensatory effects and epiphenomena. This review provides an overview of three types of human monogenic disorders that result in (1) severe, non-syndromic obesity, (2) pancreatic beta cell forms of early-onset diabetes, and (3) severe insulin resistance. In these patients with single-gene defects causing their exaggerated metabolic disorder, the primary defect is known. The lessons they provide for current understanding of the molecular pathogenesis of the common metabolic syndrome are highlighted. [ABSTRACT FROM AUTHOR]

Background: Children born small-for-gestational-age (SGA) are at increased risk of developing obesity and metabolic diseases later in life, a risk which is magnified if followed by accelerated postnatal growth. We investigated whether common gene variants associated with adult obesity were associated with increased postnatal growth, as measured by BMI z-score, in children born SGA and appropriate for gestational age (AGA) in the Auckland Birthweight Collaborative. Methods: A total of 37 candidate SNPs were genotyped on 547 European children (228 SGA and 319 AGA). Repeated measures of BMI (z-score) were used for assessing obesity status, and results were corrected for multiple testing using the false discovery rate. Results: SGA children had a lower BMI z-score than non-SGA children at assessment age 3.5, 7 and 11 years. We confirmed 27 variants within 14 obesity risk genes to be individually associated with increasing early childhood BMI, predominantly in those born AGA. Conclusions: Genetic risk variants are less important in influencing early childhood BMI in those born SGA than in those born AGA, suggesting that non-genetic or environmental factors may be more important in influencing childhood BMI in those born SGA. [ABSTRACT FROM AUTHOR]

Background: Loss of methylation (LOM) at imprinting control region (ICR) 1 or LOM at ICR 2 on chromosome 11p15 in leucocyte DNA is commonly used to diagnose the imprinting disorders Silver Russell syndrome (SRS) characterized by growth restriction or Beckwith Wiedemann syndrome (BWS) characterized by overgrowth, respectively. Case presentation: A child was normally conceived and born by caesarian section to a healthy 19 year old smoking mother (G2P1) at 38 weeks gestation, with SGA (birthweight SDS--2.44), placenta weight 250g (normal histology), with an umbilical hernia and transient neonatal hypoglycemia but no other features of BWS. The methylation status at 11p15 region was initially investigated by multiplex ligation dependent probe amplification (MLPA). Subsequently, methylation-specific (ms) PCR was performed to screen for this and other imprinted loci abnormalities at PLAG1 (6q24), IGF2R (6q27), GRB10 (7p12), PEG1/MEST (7q32), DLK1 (14q32), SNRPN (15q11); PEG3 (19q32), NESPAS/GNAS (20q13). Leucocyte DNA methylation was normal at ICR1 but markedly reduced at ICR2 using both MLPA and ms-PCR, and no other anomalies of imprinting were detected. Buccal DNA methylation was normal at all imprinted sites tested. Conclusion: This is the first report of an isolated LOM at ICR2 in leucocyte but not buccal DNA in a normally conceived singleton SGA child without overt SRS or BWS. [ABSTRACT FROM AUTHOR]

Background: Insulin like growth factor 2 (IGF2) is an imprinted gene, which has an important role in fetal growth as established in mice models. IGF2 is downregulated through hypomethylation of a differentially methylated region (DMR) in Silver Russell syndrome (SRS), characterised by growth restriction. We have previously reported that severe pre- and post-natal growth restriction associated with insulin resistance and precocious pubarche in a woman without body asymmetry or other SRS features resulted from a balanced translocation affecting the regulation of her IGF2 gene expression. We hypothesised that severe pre- and post-natal growth restriction associated with insulin resistance and precocious pubarche in the absence of SRS are also caused by downregulation of IGF2 through hypomethylation, gene mutation or structural chromosomal abnormalities. Methods: We performed routine karyotyping, IGF2 gene sequencing and investigated DNA methylation of the IGF2 differentially methylated region (DMR)0 and H19 DMR using pyrosequencing, in four women selected for very low birth weight (<−3 SDS for gestational age), precocious pubarche, short adult stature (<−2 SDS), and insulin resistance (defined as HOMA-IS < 80%); and compared their methylation results to those of 95 control subjects. Results: We identified a 20 year old woman with severe hypomethylation at both DMRs. She was the smallest at birth (birthweight SDS,-3.9), and had the shortest adult height (143 cm). The patient was diagnosed with polycystic ovarian syndrome at the age of 15 years, and had impaired fasting glucose in the presence of a low BMI (19.2 kg/m2). Conclusions: Our case of growth restriction, premature pubarche and insulin resistance in the absence of body asymmetry or other features of SRS adds to the expanding phenotype of IGF2/H19 methylation abnormalities. Further studies are needed to confirm whether growth restriction in association with premature pubarche and insulin resistance is a specific manifestation of reduced IGF2 expression. [ABSTRACT FROM AUTHOR]

Monogenic diabetes resulting from mutations that primarily reduce β-cell function accounts for 1-2% of diabetes cases, although it is often misdiagnosed as either type 1 or type 2 diabetes. Knowledge of the genetic etiology of diabetes enables more-appropriate treatment, better prediction of disease progression, screening of family members and genetic counseling. We propose that the old clinical classifications of maturity-onset diabetes of the young and neonatal diabetes are obsolete and that specific genetic etiologies should be sought in four broad clinical situations because of their specific treatment implications. Firstly, diabetes diagnosed before 6 months of age frequently results from mutation of genes that encode Kir6.2 (ATP-sensitive inward rectifier potassium channel) or sulfonylurea receptor 1 subunits of an ATP-sensitive potassium channel, and improved glycemic control can be achieved by treatment with high-dose sulfonylureas rather than insulin. Secondly, patients with stable, mild fasting hyperglycemia detected particularly when they are young could have a glucokinase mutation and might not require specific treatment. Thirdly, individuals with familial, young-onset diabetes that does not fit with either type 1 or type 2 diabetes might have mutations in the transcription factors HNF-1α (hepatocyte nuclear factor 1-α) or HNF-4α, and can be treated with lowdose sulfonylureas. Finally, extrapancreatic features, such as renal disease (caused by mutations in HNF-1β) or deafness (caused by a mitochondrial m.3243A>G mutation), usually require early treatment with insulin. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgical procedures such as laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are increasingly being utilized to manage type 2 diabetes in those with morbid obesity. It is unclear which procedure is more effective for diabetes remission. Methods: In a prospective, parallel, two-arm, study conducted in a single centre, eligible patients aged 20-55 years, with BMI 35-65kg/m2 and type 2 diabetes of at least 6 months duration were randomized 1:1 to silastic ring (SR)-LRYGB or LSG using random number codes. Patients and assessors remained blinded to treatment allocation until after primary outcome of type 2 diabetes remission was assessed at 5 years, defined by HbA1c <6% (42mmol/mol) without the use of glucose lowering medications. Results: Of the 114 patients randomized, 5 died during the 5 year follow up. Diabetes remission assessed in 108/109 (99%) patients, was achieved by 26/53 (49%) after SR-LRYGB vs. 18/55 (33%) after LSG (adjusted odds ratio 6.8; 95% confidence interval, 2.1 to 22.1, p=0.002). Percentage body weight loss assessed in 99/109 (91%) patients, was also greater after SR-LRYGB than after LSG, (26.9± 8.5% vs. 16.3±8.2%, p<0.0001). Acute, 30-day complication rates were similar in both groups. Late re-intervention rates were higher after SR-LRYGB (20 vs. 12). General health and physical functioning domains improved after both types of surgery, with greater improvements in physical functioning after SR-LRYGB (p<0.01). Conclusions: Among patients with obesity and type 2 diabetes, SR-LRYGB provides greater diabetes remission and weight loss compared to LSG at 5 years. Disclosure: R. Murphy: None. R. G. Cutfield: None. M. W. C. Booth: None. [ABSTRACT FROM AUTHOR]

Background: The complexities of mitochondrial disease make epidemiological studies challenging, yet this information is important in understanding the healthcare burden and addressing service and educational needs. Existing studies are limited to quaternary centres or focus on a single genotype or phenotype and estimate disease prevalence at 12.5 per 100 000. New Zealand's (NZ) size and partially integrated national healthcare system make it amenable to a nationwide prevalence study. Aim: To estimate the prevalence of molecularly confirmed and suspected mitochondrial disease on 31 December 2015 in NZ. Methods: Cases were identified from subspecialists and laboratory databases and through interrogation of the Ministry of Health National Minimum Dataset with a focus on presentations between 2000 and 2015. Patient records were reviewed, and those with a diagnosis of 'mitochondrial disease' who were alive and residing in NZ on the prevalence date were included. These were divided into molecularly confirmed and clinically suspected cases. Official NZ estimated resident population data were used to calculate prevalence. Results: Seven hundred twenty‐three unique national health index numbers were identified. Five hundred five were excluded. The minimum combined prevalence for mitochondrial disease was 4.7 per 100 000 (95% confidence interval (CI): 4.1–5.4). The minimum prevalence for molecularly confirmed and suspected disease was 2.9 (95% CI 2.4–3.4) and 1.8 (95% CI 1.4–2.2) cases per 100 000 respectively. Conclusions: Within the limitations of this study, comparison to similar prevalence studies performed by specialist referral centres suggests mitochondrial disease is underdiagnosed in NZ. This highlights a need for improved education and referral pathways for mitochondrial disease in NZ. [ABSTRACT FROM AUTHOR]

Assessment of senior medical students is usually calibrated at the level of achieving expected learning outcomes for graduation. Recent research reveals that clinical assessors often balance two slightly different perspectives on this benchmark. The first is the formal learning outcomes at graduation, ideally as part of a systematic, program-wide assessment approach that measures learning achievement, while the second is consideration of the candidate's contribution to safe care and readiness for practice as a junior doctor. The second is more intuitive to the workplace, based on experience working with junior doctors. This perspective may enhance authenticity in assessment decisions made in OSCEs and work-based assessments to better align judgements and feedback with professional expectations that will guide senior medical students and junior doctors' future career development. Modern assessment practices should include consideration of qualitative as well as quantitative information, overtly including perspectives of patients, employers, and regulators. This article presents 12 tips for how medical education faculty might support clinical assessors by capturing workplace expectations of first year medical graduates and develop graduate assessments based on a shared heuristic of 'work-readiness'. Peer-to-peer assessor interaction should be facilitated to achieve correct calibration that 'merges' the differing perspectives to produce a shared construct of an acceptable candidate. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) triples a person's risk of active tuberculosis (TB) and is associated with increased mortality. It is unclear whether diabetes status and/or the associated renal dysfunction is associated with poor TB outcomes in New Zealand, which has high diabetes screening. Aim: To characterise the population of TB‐DM and TB‐alone to assess the effect of diabetes status and renal function on hospitalisation and mortality. Methods: Clinical records from all adult patients diagnosed with TB in Auckland over a 6‐year period (2010–2015) were reviewed. Baseline demographics, clinical presentation and microbiological data were assessed to compare the rates of hospitalisation and mortality between those with TB‐DM and TB‐alone. Statistical significance was defined as P < 0.05. Results: A total of 701 patients was identified with TB; 120 (17%) had an unknown diabetes status and were excluded, and 135 had co‐existing diabetes. The TB‐DM and TB‐alone groups had similar distribution of TB site and proportions of Mycobacterium tuberculosis culture positivity. Univariate analysis showed TB‐DM patients had statistically significantly higher proportions of acute hospitalisation and mortality. Multivariate logistic regression showed only a reduced estimated glomerular filtration rate (eGFR) accounted for the higher rates of hospitalisation, with the odds of hospitalisation increasing by 2% for every unit decrease in eGFR. The odds of mortality increased by 6% for every year increase in age, and the odds of mortality increased by 3% for every unit reduction in eGFR. Conclusions: Diabetes is associated with higher TB hospitalisation and mortality; however, this is likely mediated by increased age and chronic kidney disease. [ABSTRACT FROM AUTHOR]

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) inflammasome pathway is believed to mediate chronic inflammation in diabetic retinopathy (DR); however, its impact on the progression of DR remains to be elucidated. Therefore, the primary aim of this pilot study was to determine whether systemic inflammasome biomarkers interleukin (IL)-1β and IL-18 can be used to predict DR progression. DR screening results were analyzed against weight, level of glycated hemoglobin (HbA1c), and plasma levels of inflammasome biomarkers (IL-1β and IL-18), as well as general inflammation markers (C-reactive protein (CRP), IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF)) in patients with type 2 diabetes at baseline and 1 year post-bariatric surgery. Cross-sectional analysis demonstrated that weight, HbA1c, CRP, and IL-18 did not correlate with DR severity. The progressed group showed a higher relative change in IL-18 and CRP levels compared to the stable and regressed groups. Furthermore, relative changes in plasma CRP levels correlated with those of IL-18. Although further validation with larger cohorts is necessary, this pilot study supports the hypothesis that systemic inflammasome activation is associated with DR progression. [ABSTRACT FROM AUTHOR]

The article discusses the impact of infants antibiotic exposure and subsequent body mass index (BMI) to children 7 years of age. It states that the fermentation activity of intestinal bacteria are changed in intrauterine growth. It also mentions that the children received antibiotics in the first year of life which is not associated with any significant difference in BMI of those born small for gestational age (SGA).

Objective: To assess diabetes eye service use in New Zealand among people aged ≥15 years by estimating service attendance, biennial screening rate, and disparities in the use of screening and treatment services. Methods: We obtained Ministry of Health data from the National Non-Admitted Patient Collection on diabetes eye service events between 1 July 2006 and 31 December 2019 and sociodemographic and mortality data from the Virtual Diabetes Register and linked these using a unique patient identifier (encrypted National Health Index). We 1) summarized attendance at retinal screening and ophthalmology services, 2) calculated biennial and triennial screening rate, 3) summarized treatment with laser and anti-VEGF and used log-binomial regression to examine associations of all of these with age group, ethnicity, and area-level deprivation. Results: In total, 245,844 people aged ≥15 years had at least one diabetes eye service appointment attended or scheduled; half of these (n = 125,821, 51.2%) attended only retinal screening, one-sixth attended only ophthalmology (n = 35,883, 14.6%) and one-third attended both (n = 78,300, 31.8%). The biennial retinal screening rate was 62.1%, with large regional variation (73.9% in Southern District to 29.2% in West Coast). Compared with NZ Europeans, Māori were approximately twice as likely to never receive diabetes eye care or to access ophthalmology when referred from retinal screening, 9% relatively less likely to receive biennial screening and received the fewest anti-VEGF injections when treatment was commenced. Disparities in service access were also present for Pacific Peoples compared to NZ Europeans, younger and older age groups compared to those aged 50–59 years and those living in areas with higher deprivation. Conclusions: Access to diabetes eye care is suboptimal, with substantial disparity between age groups, ethnicity groups, area level deprivation quintile and across districts. Efforts to improve access to and quality of diabetes eye care services must include strengthening data collection and monitoring. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. Methods: A 19‐variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex‐stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. Results: The PRS was associated with earlier age at gout onset in men (β = –3.61 in years per unit PRS [95% confidence interval (95% CI) –4.32, –2.90] in European men; β = –6.35 [95% CI –8.91, –3.80] in East Polynesian men; β = –3.51 [95% CI –5.46, –1.57] in West Polynesian men) but not in women (β = 0.07 [95% CI –2.32, 2.45] in European women; β = 0.20 [95% CI –7.21, 7.62] in East Polynesian women; β –3.33 [95% CI –9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (β = –2.42 [95% CI –3.37, –1.46] and β = –6.80 [95% CI –10.06, –3.55], respectively) but not in West Polynesian men (β = –1.79 [95% CI –4.74, 1.16]). Conclusion: Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups. [ABSTRACT FROM AUTHOR]

Objective: While there is an emerging role of pancreatic fat in the aetiology of type 2 diabetes mellitus (T2DM), its impact on the associated decrease in insulin secretion remains controversial. We aimed to determine whether pancreatic fat negatively affects β-cell function and insulin secretion in women with overweight or obesity but without T2DM. Methods: 20 women, with normo- or dysglycaemia based on fasting plasma glucose levels, and low (< 4.5%) vs high (≥ 4.5%) magnetic resonance (MR) quantified pancreatic fat, completed a 1-hr intravenous glucose tolerance test (ivGTT) which included two consecutive 30-min square-wave steps of hyperglycaemia generated by using 25% dextrose. Plasma glucose, insulin and C-peptide were measured, and insulin secretion rate (ISR) calculated using regularisation deconvolution method from C-peptide kinetics. Repeated measures linear mixed models, adjusted for ethnicity and baseline analyte concentrations, were used to compare changes during the ivGTT between high and low percentage pancreatic fat (PPF) groups. Results: No ethnic differences in anthropomorphic variables, body composition, visceral adipose tissue (MR-VAT) or PPF were measured and hence data were combined. Nine women (47%) were identified as having high PPF values. PPF was significantly associated with baseline C-peptide (p = 0.04) and ISR (p = 0.04) in all. During the 1-hr ivGTT, plasma glucose (p<0.0001), insulin (p<0.0001) and ISR (p = 0.02) increased significantly from baseline in both high and low PPF groups but did not differ between the two groups at any given time during the test (PPF x time, p > 0.05). Notably, the incremental areas under the curves for both first and second phase ISR were 0.04 units lower in the high than low PPF groups, but this was not significant (p > 0.05). Conclusion: In women with overweight or obesity but without T2DM, PPF did not modify β-cell function as determined by ivGTT-assessed ISR. However, the salient feature in biphasic insulin secretion in those with ≥4.5% PPF may be of clinical importance, particularly in early stages of dysglycaemia may warrant further investigation. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the role of nucleotide-binding oligomerization domain- (NOD-) like receptor (NLR) protein 3 (NLRP3) inflammasome activation in the onset of diabetic retinopathy (DR) using retina and vitreous from donors without diabetes mellitus (CTL), with diabetes mellitus alone (DM), and with DR. Retinal expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1), the key markers of retinal inflammation, connexin43 (Cx43) which is involved in upstream inflammasome regulation, as well as NLRP3 and cleaved caspase-1, the main markers of inflammasome activation, were evaluated using immunohistochemistry and Western blotting. Vitreous interleukin (IL)-1β and IL-18, biomarkers of the activated inflammasome, were measured using a Luminex multiplex assay. Results showed a significant increase in the number and size of Iba-1+ cells and NLRP3 expression in DM, while a significant increase in GFAP, Cx43, cleaved caspase-1 and vitreous IL-18, as well as a further increase in Iba-1 and NLRP3 was found in DR. This suggests that the inflammasome is already primed in DM before its activation in DR. Furthermore, IL-18 may act as the major effector of inflammasome activation in DR while nuclear translocation of cleaved caspase-1 may play a role in gene transcription contributing to DR onset. [ABSTRACT FROM AUTHOR]

Maternal stress during pregnancy has been associated with a range of adverse outcomes in offspring and the catechol-O-methyltransferase (COMT) gene has been linked to differential susceptibility to the consequences of antenatal stress. This study examined two functional polymorphisms of the COMT gene (rs4680 and rs165599) in relation to maternal perceived stress and childhood cognitive performance. Data from the longitudinal Auckland Birthweight Collaborative (ABC) study was used. Maternal perceived stress over the prior month was measured at birth, 3.5 and 7years. Full-Scale IQ (FSIQ) was measured at ages 7 and 11. At age 11, a total of 546 DNA samples were collected from the child participants. Data were subjected to a series of split-plot ANCOVAs with birthweight for gestational age and maternal school leaving age as covariates. There were direct effects of maternal stress during the last month of pregnancy on offspring FSIQ at ages 7 and 11years. A significant interaction revealed that children exposed to high maternal antenatal stress had significantly lower FSIQ scores at both 7 and 11years of age than those exposed to low stress, only when they were carriers of the rs165599 G allele. At each age, this difference was of approximately 5 IQ points. The G allele of the rs165599 polymorphism may confer genetic susceptibility to negative cognitive outcomes arising from exposure to antenatal stress. This finding highlights the need to consider gene-environment interactions when investigating the outcomes of antenatal stress exposure. [ABSTRACT FROM AUTHOR]

Background: Historically, geneticists have relied on genotyping arrays and imputation to study human genetic variation. However, an underrepresentation of diverse populations has resulted in arrays that poorly capture global genetic variation, and a lack of reference panels. This has contributed to deepening global health disparities. Whole genome sequencing (WGS) better captures genetic variation but remains prohibitively expensive. Thus, we explored WGS at "mid-pass" 1-7x coverage. Results: Here, we developed and benchmarked methods for mid-pass sequencing. When applied to a population without an existing genomic reference panel, 4x mid-pass performed consistently well across ethnicities, with highc recall (98%) and precision (97.5%). Conclusion: Compared to array data imputed into 1000 Genomes, mid-pass performed better across all metrics and identified novel population-specific variants with potential disease relevance. We hope our work will reduce financial barriers for geneticists from underrepresented populations to characterize their genomes prior to biomedical genetic applications. [ABSTRACT FROM AUTHOR]

Background: Historically, geneticists have relied on genotyping arrays and imputation to study human genetic variation. However, an underrepresentation of diverse populations has resulted in arrays that poorly capture global genetic variation, and a lack of reference panels. This has contributed to deepening global health disparities. Whole genome sequencing (WGS) better captures genetic variation but remains prohibitively expensive. Thus, we explored WGS at "mid-pass" 1-7x coverage. Results: Here, we developed and benchmarked methods for mid-pass sequencing. When applied to a population without an existing genomic reference panel, 4x mid-pass performed consistently well across ethnicities, with high recall (98%) and precision (97.5%). Conclusion: Compared to array data imputed into 1000 Genomes, mid-pass performed better across all metrics and identified novel population-specific variants with potential disease relevance. We hope our work will reduce financial barriers for geneticists from underrepresented populations to characterize their genomes prior to biomedical genetic applications. [ABSTRACT FROM AUTHOR]

The long-term impact of a father's involvement in offspring development is understudied. The current study investigated the relations between early paternal engagement (i.e., the amount of time fathers engaged in one-to-one activity with their child), paternal accessibility (i.e., fathers' physical proximity to their children) and later child behavioral difficulties. Data were obtained from five phases of the Auckland Birthweight Collaborative (ABC) longitudinal cohort study: at the study children's birth; at 12 months; 3.5 years; 7 years; and 11 years of age. Moderated linear regression analyses revealed that there was a negative, long-term effect of paternal departure from the family household (i.e., reduced paternal accessibility) by 3.5 years of age on children's total behavioral difficulties and conduct problems scores, but only if departed fathers had been highly engaged during the child's first year of life. These findings suggest that the relationship between paternal accessibility and paternal engagement is potentially more nuanced than previously thought. [ABSTRACT FROM AUTHOR]

Background: Individuals born small for gestational age (SGA) are at increased risk of rapid postnatal weight gain, later obesity and diseases in adulthood such as type 2 diabetes, hypertension and cardiovascular diseases. Environmental risk factors for SGA are well established and include smoking, low pregnancy weight, maternal short stature, maternal diet, ethnic origin of mother and hypertension. However, in a large proportion of SGA, no underlying cause is evident, and these individuals may have a larger genetic contribution. Methods: In this study we tested the association between SGA and polymorphisms in genes that have previously been associated with obesity and/or diabetes. We undertook analysis of 54 single nucleotide polymorphisms (SNPs) in 546 samples from the Auckland Birthweight Collaborative (ABC) study. 227 children were born small for gestational age (SGA) and 319 were appropriate for gestational age (AGA). Results and Conclusion: The results demonstrated that genetic variation in KCNJ11, BDNF, PFKP, PTER and SEC16B were associated with SGA and support the concept that genetic factors associated with obesity and/or type 2 diabetes are more prevalent in those born SGA compared to those born AGA. We have previously determined that environmental factors are associated with differences in birthweight in the ABC study and now we have demonstrated a significant genetic contribution, suggesting that the interaction between genetics and the environment are important. [ABSTRACT FROM AUTHOR]

Background: Until recently, most patients with diabetes worldwide have been diagnosed when symptomatic and have high cardiovascular risk, meaning most should be prescribed cardiovascular preventive medications. However, in New Zealand, a world-first national programme led to approximately 90% of eligible adults being screened for diabetes by 2016, up from 50% in 2012, identifying many asymptomatic patients with recent-onset diabetes. We hypothesised that cardiovascular risk prediction equations derived before widespread screening would now significantly overestimate risk in screen-detected patients.Methods: New Zealanders aged 30-74 years with type 2 diabetes and without known cardiovascular disease, heart failure, or substantial renal impairment were identified from the 400 000-person PREDICT primary care cohort study between Oct 27, 2004, and Dec 30, 2016, covering the period before and after widespread screening. Sex-specific equations estimating 5-year risk of cardiovascular disease were developed using Cox regression models, with 18 prespecified predictors, including diabetes-related and renal function measures. Equation performance was compared with an equivalent equation derived in the New Zealand Diabetes Cohort Study (NZDCS), which recruited between 2000 and 2006, before widespread screening.Findings: 46 652 participants were included in the PREDICT-1° Diabetes subcohort, of whom 4114 experienced first cardiovascular events during follow-up (median 5·2 years, IQR 3·3-7·4). 14 829 (31·8%) were not taking oral hypoglycaemic medications or insulin at baseline. Median 5-year cardiovascular risk estimated by the new equations was 4·0% (IQR 2·3-6·8) in women and 7·1% (4·5-11·2) in men. The older NZDCS equation overestimated median cardiovascular risk by three times in women (median 14·2% [9·7-20·0]) and two times in men (17·1% [4·5-20·0]). Model and discrimination performance measures for PREDICT-1° Diabetse equations were also significantly better than for the NZDCS equation (eg, for women: R2=32% [95% CI 29-34], Harrell's C=0·73 [0·72-0·74], Royston's D=1·410 [1·330-1·490] vs R2=24% [21-26], C=0·69 [0·67-0·70], and D=1·147 [1·107-1·187]).Interpretation: International treatment guidelines still consider most people with diabetes to be at high cardiovascular risk; however, we show that recent widespread diabetes screening has radically changed the cardiovascular risk profile of people with diabetes in New Zealand. Many of these patients have normal renal function, are not dispensed glucose-lowering medications, and have low cardiovascular risk. These findings have clear international implications as increased diabetes screening is inevitable due to increasing obesity, simpler screening tests, and the introduction of new-generation glucose-lowering medications that prevent cardiovascular events. Cardiovascular risk prediction equations derived from contemporary diabetes populations, with multiple diabetes-related and renal function predictors, will be required to better differentiate between low-risk and high-risk patients in this increasingly heterogeneous population and to inform appropriate non-pharmacological management and cost-effective targeting of expensive new medications.Funding: Health Research Council of New Zealand, Heart Foundation of New Zealand, and Healthier Lives National Science Challenge. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the validity of the Strengths and Difficulties Questionnaire in a cohort of New Zealand children followed from birth to the age of eleven. The study also aimed to assess the stability of the child data in relation to behavioural outcomes during this period. Methods: Children in the Auckland Birthweight Collaborative Study were assessed at approximately 3½, 7 and 11 years of age. At all time-points parents completed the parent version of the Strengths and Difficulties Questionnaire, and the children themselves completed the self-report version at 11 years of age. The validity and internal consistency were assessed using exploratory factor analysis, Cronbach's alpha, and McDonald's Omega. Cross tabulations and Chi-square statistics were used to determine whether Total Difficulty scores, as per accepted cut-offs, remained stable over time (between normal and abnormal/borderline categories). Results: The factor structure remained relatively consistent across all three time-points, though several questions did not load as per the originally published factor analysis at the earliest age. The internal consistency of the Strengths and Difficulties Questionnaire was good at all time-points and for parent- and child-completed versions. There was low agreement in the total scores between time points. Conclusions: The factor analysis shows that the Strengths and Difficulties Questionnaire has a similar factor structure, particularly in older ages, to that previously published and shows good internal consistency. At the pre-school follow up, a larger than expected proportion of children were identified with high scores, particularly in the conduct sub-scale. Children's behaviour changes over time, with only poor to moderate agreement between those identified as abnormal or borderline over the longitudinal follow up. [ABSTRACT FROM AUTHOR]

Individualised management of obesity remains challenging and, to date, most treatment is based on clinical judgement. This study aimed to develop and validate a novel questionnaire-based tool to identify three pre-defined eating behavior (EB) traits, emotional eating, reduced satiety (constant hunger) and reduced satiation (feasters) that may predict selective medication response given their targeted actions. We recruited 977 individuals from a tertiary academic diabetes clinic to participate in this two-phase validation study. Participants self-reported weight management activities and were asked to self-assess their EB characteristics. The initial questionnaire included 42 visual analogue scale questions. In Phase I, 729 participants completed the questionnaire, including Māori (11.8%) and Pacific peoples (19.3%). After random division of the study sample, Exploratory Factor Analysis (EFA) confirmed a three-factor model as the best fit. Stepwise removal of items with inadequate factor loading retained 27 of 42 items, which accounted for 96% of the variance. Confirmatory Factor Analysis (CFA), performed on the second half of the sample, demonstrated good model fit with the final 27-item questionnaire. Internal consistency was high for factor (α = 0.82–0.95) and demographic subgroups, and similar to those obtained in the EFA. Test-retest reliability in a subset of 399 participants who repeated the questionnaire after a four-week interval (Phase II) showed moderate to good reliability. Participants classified into one of three EB types based on the highest median score among the factors. Test-retest reliability was robust for emotional eaters (71.25%) and constant hunger (68.9%). The correlation between aggregate EB score (sum of three EB scores) and BMI was significant (Spearman rho = 0.314, P =.0005). The questionnaire reliably identified three distinct EB traits, which may be informative for precision medicine applications for obesity management. [ABSTRACT FROM AUTHOR]

Aim: To examine early adolescent physical activity and risk of later depressive symptoms at age 16 years in a prospective cohort study.Methods: Participants were children and parents enrolled at birth of the child. Approximately half the children enrolled in the Auckland Birthweight Collaborative Study were small for gestational age at birth (SGA ≤10th percentile for sex and gestation) and half were appropriate for gestational age (AGA >10th percentile). Maternal demographic data were collected at birth, and children were followed through to age 16 years. Depression at 16 was assessed using the Center for Epidemiological Studies Depression Scale for Children. Accelerometer measures of physical activity and sleep were measured at 11 years of age.Results: Moderate to severe depression was present in 15.6% of the 467 16-year-olds. Objectively measured physical activity and sleep at 11 years were not significantly associated with depressive symptoms at 16 years of age.Conclusion: Prospectively collected objective measures of physical activity levels and sleep were not predictive of depressive symptoms later in adolescence in a healthy community cohort. While interventions to promote increased physical activity and sleep in adolescents who are depressed may be effective, physical activity and sleep in the general population of adolescents does not protect against future depression. [ABSTRACT FROM AUTHOR]

To examine differences in incidence, prevalence and screening for diabetic retinopathy in New Zealand, we searched MEDLINE, EMBASE and CINAHL up to 6 December 2018 for observational studies reporting diabetic eye disease or attendance at retinal screening, disaggregated by ethnicity. Two authors separately screened and selected studies, and extracted data. None of the 11 included studies reported data on visual impairment from diabetic retinopathy. All nine studies reporting diabetic eye disease by ethnicity found Pacific people and Māori had higher rates of sight‐threatening disease and lower rates of screening attendance compared to Europeans. Data for Asian people were infrequently reported, but when they were, they also fared worse than Europeans. This review highlights that equity‐focused strategies are needed to address ethnic disparities in eye health among New Zealanders with diabetes. The review also identifies how research methods can be strengthened to enable future calculation of robust disease prevalence estimates. [ABSTRACT FROM AUTHOR]

It is not clear whether there are differences in proportions of fat loss from visceral:subcutaneous depots by probiotic supplementation, ethnicity or sex during weight loss; or whether visceral/pancreatic fat depot changes are related to changes in HbA1c. Our objective is to investigate whether weight loss from different fat depots is related to these factors during weight loss achieved by intermittent fasting. Prediabetes participants on 5:2 intermittent fasting were randomized 1:1 to either daily probiotic or placebo for 12 weeks. Twenty-four patients had magnetic resonance imaging data at baseline and 12 weeks. After 12 weeks of intermittent fasting, subcutaneous fat (%) changed from 35.9 ± 3.1 to 34.4 ± 3.2, visceral fat (%) from 15.8 ± 1.3 to 14.8 ± 1.2, liver fat (%) from 8.7 ± 0.8 to 7.5 ± 0.7 and pancreatic fat (%) from 7.7 ± 0.5 to 6.5 ± 0.5 (all p < 0.001). Changes in weight, HbA1c, SAT, VAT, LF and PF did not differ significantly between probiotic and placebo groups. Overall weight loss was correlated with fat loss from subcutaneous depots. Losses from different fat depots did not correlate with changes in HbA1c or differ by probiotic supplementation, ethnicity or sex. [ABSTRACT FROM AUTHOR]

Objective: To evaluate diabetes remission after bariatric surgery by presence of GAD antibody among those with obesity and type 2 diabetes (T2D).Research Design and Methods: Screening GAD was performed in 221 patients with T2D and obesity referred for bariatric surgery. Nine of 16 patients with GAD and 112 of 205 without GAD proceeded with surgery. Diabetes remission and weight loss were compared by GAD presence.Results: The group with GAD had levels 16-91 IU/mL. Those with and without GAD were similar with regard to age, BMI, diabetes duration, proportion treated with insulin, HbA1c, and C-peptide (1,354 ± 548 vs. 1,358 ± 487 pmol/L). At 1 and 5 years postoperatively, the two groups achieved similar BMI reduction and diabetes remission (67% vs. 73%, P = 0.71, and 56% vs. 57%, P = 1.0).Conclusions: Low-titer GAD in patients with T2D and retained C-peptide should not be a deterrent for bariatric surgery when the principal aim is diabetes remission. [ABSTRACT FROM AUTHOR]

Abstract Background Previous studies indicate that low birth weight and exposure to maternal stress during pregnancy may result in shortened telomeres in infants. Shorter telomere length has in turn been linked with accelerated ageing and with age-related diseases. This study aimed to investigate the association between pregnancy and birth factors and relative telomere length in offspring at 11 years of age. Methods Participants were aged 11 years enrolled in the Auckland Birthweight Collaborative Study at birth (n = 380). Half of the children were born small for gestational age (SGA = birthweight ≤ 10th percentile) and half were appropriate for gestational age (AGA = birthweight > 10th percentile). Maternal stress during pregnancy was assessed using the Perceived Stress Scale. Relative leukocyte telomere length (RTL) in leukocytes was measured at 11 years of age using quantitative real-time PCR. Results RTL was normally distributed (mean = 3.78, SD = 1.05). There were no significant associations between RTL at age 11 years and birthweight, sex, maternal smoking, maternal stress during pregnancy or maternal pre-pregnancy body mass index. Conclusion At age 11 years, RTL did not differ between children by birthweight or pregnancy-related stressors. Further telomere-related studies in newborns, children and adolescents are merited to increase knowledge of potential telomere modulating factors. Highlights • Telomere length was assessed in 336 children aged 11 years from a longitudinal cohort. • Telomere length did not differ by birthweight or antenatal maternal stress exposure. • Telomere length studies across childhood will help to understand modulating factors. [ABSTRACT FROM AUTHOR]

Background: In New Zealand, it is recommended that all pregnant women have a haemoglobin A1c (HbA1c) test performed with their booking antenatal bloods to identify previously unrecognised diabetes. However, screening rates in some groups are low. Use of a point‐of‐care device may improve compliance with screening. Aim: To assess the accuracy of the COBAS b101 point‐of‐care system referenced against a laboratory method, for measurement of HbA1c levels in pregnant women. Materials and methods: Convenience sample of 40 obese pregnant women enrolled in a clinical trial. HbA1c was assayed in paired capillary and venous whole blood samples using the COBAS b101 point‐of‐care system and Primus Ultra2 high performance liquid chromatography laboratory analyser, respectively. The accuracy of the point‐of‐care system was assessed by Bland–Altman analysis. Results: The mean (SD) laboratory HbA1c was 35.9 (2.0) mmol/mol. The COBAS b101 point‐of‐care system, compared with the laboratory reference method, had a small negative bias for HbA1c (−1.0 mmol/mol, 95% CI −2.0 to −0.03, P = 0.03) and relatively wide 95% limits of agreement (−7.2 to 5.1 mmol/mol). Conclusion: In conclusion, we found that in pregnancy, the COBAS b101 point‐of‐care system has a small negative bias and modest point accuracy for HbA1c. When used to screen for previously unrecognised diabetes in pregnancy, appropriate COBAS b101 HbA1c point‐of‐care HbA1c thresholds for a negative and positive result are 7 mmol/mol below and 5 mmol/mol above the clinical threshold, respectively. Values between these limits should be confirmed by laboratory testing. [ABSTRACT FROM AUTHOR]

Background: In a two‐centre randomized placebo‐controlled trial of Lactobacillus rhamnosus HN001 (HN001) (6 × 109 colony‐forming units [cfu]) or Bifidobacterium lactis HN019 (HN019) (9 × 109 cfu) taken daily from 35‐week gestation to 6 months' post‐partum in mothers while breastfeeding and from birth to age 2 years in infants, we showed that HN001 significantly protected against eczema development at 2, 4 and 6 years and atopic sensitization at 6 years. There was no effect of HN019. We report here the findings for 11 year outcomes. Methods: At age 11 years, eczema was defined as previously using the UK Working Party's Diagnostic Criteria. Asthma, wheeze, hay fever and rhinitis were defined based on the International Study of Asthma and Allergies in Childhood (ISAAC) questions. Atopic sensitization was defined as one or more positive responses (mean wheal diameter ≥3 mm) to a panel of food and aeroallergens. Analysis was intention‐to‐treat using hazard ratios to assess probiotic effects on the 11‐year lifetime prevalence and relative risks for point or 12‐month prevalence at 11 years. Results: Early childhood HN001 supplementation was associated with significant reductions in the 12‐month prevalence of eczema at age 11 years (relative risk [RR] = 0.46, 95% CI 0.25‐0.86, P = 0.015) and hay fever (RR = 0.73, 95% CI 0.53‐1.00, P = 0.047). For the lifetime prevalence, HN001 was associated with a significant reduction in atopic sensitization (hazard ratio [HR] = 0.71, 95% CI 0.51‐1.00, P = 0.048), eczema (HR = 0.58, 95% CI 0.41‐0.82, P = 0.002) and wheeze (HR = 0.76, 95% CI 0.57‐0.99, P = 0.046). HN019 had no significant effect on these outcomes. Conclusion: This is the first early probiotic intervention to show positive outcomes for at least the first decade of life across the spectrum of allergic disease. [ABSTRACT FROM AUTHOR]

A father’s presence in the family is important for promoting adaptive behavioral functioning in children. It is unknown however, if there is a critical time during infancy and childhood for such paternal presence and involvement to affect behaviour. Using data from the Auckland Birthweight Collaborative (ABC) study, we examined the amount of paternal presence children experienced through their first 11 years of life (measured as fathers’ time spent in the same household as their children) and its effect on their behavioral outcomes at 11 years of age. After controlling for potential confounds, children who whose fathers were minimally present (left between 0 and 3.5 years of age) were twice as likely to report clinically significant behavioural difficulties as those whose fathers were present throughout childhood. Those whose fathers were present for early childhood (left between 3.5 and 7 years of age) exhibited no significant differences in their behaviour at 11 years of age when compared to their peers whose fathers remained present. Mothers reported no significant changes in their children’s behavior. Findings suggested that paternal presence early in a child’s life might be most important with regard to promoting adaptive behavioural functioning as they age. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in PPARG cause familial partial lipodystrophy type 3 (FPLD3) and severe metabolic disease in many patients. Missense mutations in PPARG are present in ∼1 in 500 people. Although mutations are often binarily classified as benign or deleterious, prospective functional classification of all missense PPARG variants suggests that their impact is graded. Furthermore, in testing novel mutations with both prototypic endogenous (e.g., prostaglandin J2 [PGJ2]) and synthetic ligands (thiazolidinediones, tyrosine agonists), we observed that synthetic agonists selectively rescue function of some peroxisome proliferator-activated receptor-γ (PPARγ) mutants. We report on patients with FPLD3 who harbor two such PPARγ mutations (R308P and A261E). Both PPARγ mutants exhibit negligible constitutive or PGJ2-induced transcriptional activity but respond readily to synthetic agonists in vitro, with structural modeling providing a basis for such differential ligand-dependent responsiveness. Concordant with this finding, dramatic clinical improvement was seen after pioglitazone treatment of a patient with R308P mutant PPARγ. A patient with A261E mutant PPARγ also responded beneficially to rosiglitazone, although cardiomyopathy precluded prolonged thiazolidinedione use. These observations indicate that detailed structural and functional classification can be used to inform therapeutic decisions in patients with PPARG mutations. [ABSTRACT FROM AUTHOR]

Background: The increasing prevalence of overweight and obesity in childhood has implications for their future health. There are many potential contributors to overweight and obesity in childhood. The aim was to investigate the association between postulated risk factors and body mass index (BMI) in children and adolescents. Methods: Secondary analysis of data from a multi-centre, multi-country, cross-sectional study (ISAAC Phase Three). Parents/guardians of children aged 6–7 years completed a questionnaire about their child’s current height and weight, and the postulated risk factors. Adolescents aged 13–14 years reported their own height and weight and answered questions about the postulated risk factors. A general linear mixed model was used to determine the association between BMI and the postulated risk factors. Imputation was used if there were missing responses for 3 or fewer explanatory variables. Results: 65,721 children (27 centres, 15 countries) and 189,282 adolescents (70 centres, 35 countries) were included in the final analyses. Many statistically significant associations were identified, although for most variables the effect sizes were small. In children birth weight (for each kg increase in birth weight the BMI increased by +0.43 kg/m2, p<0.001), television viewing (5+ hours/day +0.33 kg/m2 vs. <1 hour/day, p<0.001), fast food (≥3 times/week +0.16 kg/m2 vs. never, p<0.001) vigorous physical activity (3+ hours/week 0.071 kg/m2 vs. never, p = 0.023) and maternal smoking in the first year of life (+0.13 kg/m2, p<0.001) were associated with a higher BMI in the adjusted model. Nut consumption (≥3 times/week -0.11 kg/m2 vs. never, p = 0.002) was associated with a lower BMI. Early life exposures (antibiotics, paracetamol and breast feeding) were also associated with BMI. For adolescents statistically significant associations with BMI and were seen with maternal smoking (+0.25 kg/m2, p<0.001), television viewing (5+ hours/day +0.23 kg/m2 vs. <1 hour/day, p<0.001), fast food (≥3 times/week -0.19 kg/m2 vs. never, p<0.001), vigorous physical activity (3+ hours/week 0.047 kg/m2 vs. never, p<0.001) and nuts (≥3 times/week -0.22 kg/m2 vs. never, p<0.001). Conclusions: Although several early life exposures were associated with small differences in BMI, most effect sizes were small. Larger effect sizes were seen with current maternal smoking, television viewing (both with higher BMI) and frequent nut consumption (lower BMI) in both children and adolescents, suggesting that current behaviours are more important than early exposures. Although many variables may influence BMI in childhood, the putative factors studied are not of sufficient magnitude to support major public health interventions. [ABSTRACT FROM AUTHOR]

Abstract: Background: In a randomized placebo‐controlled trial, we previously found that the probiotic Lactobacillus rhamnosus HN001 (HN001) taken by mothers from 35 weeks of gestation until 6 months post‐partum if breastfeeding and their child from birth to age 2 years halved the risk of eczema during the first 2 years of life. We aimed to test whether maternal supplementation alone is sufficient to reduce eczema and compare this to our previous study when both the mother and their child were supplemented. Methods: In this 2‐centre, parallel double‐blind, randomized placebo‐controlled trial, the same probiotic as in our previous study (HN001, 6 × 109 colony‐forming units) was taken daily by mothers from 14‐16 weeks of gestation till 6 months post‐partum if breastfeeding, but was not given directly to the child. Women were recruited from the same study population as the first study, where they or their partner had a history of treated asthma, eczema or hay fever. Results: Women were randomized to HN001 (N = 212) or placebo (N = 211). Maternal‐only HN001 supplementation did not significantly reduce the prevalence of eczema, SCORAD ≥ 10, wheeze or atopic sensitization in the infant by 12 months. This contrasts with the mother and child intervention study, where HN001 was associated with reductions in eczema (hazard ratio (HR): 0.39, 95% CI 0.19‐0.79, P = .009) and SCORAD (HR = 0.61, 95% 0.37‐1.02). However, differences in the HN001 effect between studies were not significant. HN001 could not be detected in breastmilk from supplemented mothers, and breastmilk TGF‐β/IgA profiles were unchanged. Conclusion: Maternal probiotic supplementation without infant supplementation may not be effective for preventing infant eczema. [ABSTRACT FROM AUTHOR]

Objectives: Modern technology may have desensitised the 'biological clock' to environmental cues, disrupting the appropriate co-ordination of metabolic processes. Susceptibility to misalignment of circadian rhythms may be partly genetically influenced and effects on sleep quality and duration could predispose to poorer health outcomes. Shorter sleep duration is associated with obesity traits, which are brought on by an increased opportunity to eat and/or a shift of hormonal profile promoting hunger. We hypothesised that increased sleep duration will offset susceptible genetic effects, resulting in reduced obesity risk.Methods: We recruited 643 (male: 338; female: 305) European children born to participants in the New Zealand centre of the International Screening for Pregnancy Endpoints sleep study. Ten genes directly involved in the circadian rhythm machinery and a further 20 genes hypothesised to be driven by cyclic oscillations were evaluated by Sequenom assay. Multivariable regression was performed to test the interaction between gene variants and average sleep length (derived from actigraphy), in relation to obesity traits (body mass index (BMI) z-scores and percentage body fat (PBF)).Results: No association was found between average sleep length and BMI z-scores (p = 0.056) or PBF (p = 0.609). Uncorrected genotype associations were detected between STAT-rs8069645 (p = 0.0052) and ADIPOQ-rs266729 (p = 0.019) with differences in average sleep duration. Evidence for uncorrected gene-by-sleep interactions of the CLOCK-rs4864548 (p = 0.0039), PEMT-936108 (p = 0.016) and GHRELIN-rs696217 (p = 0.046) were found in relation to BMI z-scores but not for PBF.Conclusion: Our results indicate that children may have different genetic susceptibility to the effects of sleep duration on obesity. Further confirmatory studies are required in other population cohorts of different age groups. [ABSTRACT FROM AUTHOR]

Aim: To examine the relationship between reported vigorous physical activity (VPA) and body mass index (BMI) in children (6-7 years) and adolescents (13-14 years).Methods: In the International Study of Asthma and Allergies in Childhood Phase Three, 75 895 children's parents and 199 502 adolescents answered questions relating to VPA, height and weight. The association between VPA and BMI was analysed using general linear models, adjusting for country gross national index.Results: Compared to children who undertook no VPA, those in the infrequent group (once or twice per week) and those in the frequent group (three or more times per week) had mean (95% CI) BMI values 0.07 kg/m2 (0.03-0.11) and 0.09 kg/m2 (0.03-0.15) greater, respectively (p = 0.001). Compared to adolescents reporting no VPA, those in the infrequent group had a BMI 0.19 kg/m2 (0.15-0.23) greater while those in the frequent group had a BMI 0.01 kg/m2 (-0.03-0.05) greater (p < 0.0001).Conclusion: Reported VPA is not associated with lower BMI among children and adolescents. Investigation of VPA and BMI may be best undertaken in conjunction with other variables in the energy expenditure equation. A focus on VPA alone may be an inefficient way to manage BMI. [ABSTRACT FROM AUTHOR]

Aim: There may be a link between disruption to the gut microbiota in early life and later neurocognitive outcomes. We hypothesised that antibiotic use in early life is associated with a detrimental effect on later neurocognitive outcomes.Methods: Eight hundred and seventy-one European mothers and their children enrolled in the Auckland Birthweight Collaborative Study at birth. Information on antibiotic use during the first year of life and between 12 months and three-and-a-half years of age was gathered via maternal interview. Intelligence test scores and measures of behavioural difficulties were obtained when children were three-and-a-half years, seven years and 11 years of age.Results: Antibiotic use in the first year of life was reported in 70% of the 526 children with antibiotic data assessed at age three-and-a-half years. Those who had received antibiotics had more behavioural difficulties and more symptoms of depression at follow-up. Results were consistent across all standardised psychologist administered tests, as well as parent rated, teacher rated and self-report measures.Conclusion: This study demonstrates an association between antibiotic use in the first year of life and subsequent neurocognitive outcomes in childhood. If confirmed by further research, these findings could have implications for the use of antibiotics for minor illnesses in infancy. [ABSTRACT FROM AUTHOR]

Maternal stress during pregnancy has been associated with detrimental cognitive developmental outcomes in offspring. This study investigated whether antenatal maternal perceived stress and variants of the rs12193738 and rs2179515 polymorphisms on the KIAA0319 gene interact to affect reading ability and full-scale IQ (FSIQ) in members of the longitudinal Auckland Birthweight Collaborative study. Antenatal maternal stress was measured at birth, and reading ability was assessed at ages 7 and 16. Reading data were available for 500 participants at age 7 and 479 participants at age 16. FSIQ was measured at ages 7 and 11. At age 11, DNA samples were collected. Analyses of covariance revealed that individuals with the TT genotype of the rs12193738 polymorphism exposed to high maternal stress during pregnancy possessed significantly poorer reading ability (as measured by Woodcock-Johnson Word Identification standard scores) during adolescence compared with TT carriers exposed to low maternal stress. TT carriers of the rs12193738 SNP also obtained lower IQ scores at age 7 than C allele carriers. These findings suggest that the KIAA0319 gene is associated with both reading ability and general cognition, but in different ways. The effect on IQ appears to occur earlier in development and is transient, whereas the effect of reading ability occurs later and is moderated by antenatal maternal stress. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]