Publications by authors named "Benjamin B Albert"

38 Publications

Supplementation with milk enriched with complex lipids during pregnancy: A double-blind randomized controlled trial.

PLoS One 2021 24;16(2):e0244916. Epub 2021 Feb 24.

College of Life Sciences, University of Leicester, Leicester, United Kingdom.

Background: Gangliosides are a class of sphingolipids that are present in the cell membranes of vertebrates. Gangliosides influence a broad range of cellular processes through effects on signal transduction, being found abundantly in the brain, and having a role in neurodevelopment.

Objective: We aimed to assess the effects of maternal daily consumption of ganglioside-enriched milk vs non-enriched milk and a non-supplemented group of pregnant women on maternal ganglioside levels and pregnancy outcomes.

Design: Double-blind parallel randomized controlled trial.

Methods: 1,500 women aged 20-40 years were recruited in Chongqing (China) between 11 and 14 weeks of a singleton pregnancy, and randomized into three groups: Control-received standard powdered milk formulation (≥4 mg gangliosides/day); Complex milk lipid-enhanced (CML-E) group-same formulation enriched with complex milk lipids (≥8 mg gangliosides/day) from milk fat globule membrane; Reference-received no milk. Serum ganglioside levels were measured in a randomly selected subsample of 250 women per group.

Results: CML-E milk was associated with marginally greater total gangliosides levels in maternal serum compared to Control (13.02 vs 12.69 μg/ml; p = 0.034) but not to Reference group. CML-E milk did not affect cord blood ganglioside levels. Among the 1500 women, CML-E milk consumption was associated with a lower rate of gestational diabetes mellitus than control milk [relative risk 0.80 (95% CI 0.64, 0.99)], but which was not different to the Reference group. CML-E milk supplementation had no other effects on maternal or newborn health.

Conclusions: Maternal supplementation with milk fat globule membrane, as a source of gangliosides, was not associated with any adverse health outcomes, and did not increase serum gangliosides compared with the non-supplemented reference group.

Trial Registration: Chinese Clinical Trial Register (ChiCTR-IOR-16007700).

Clinical Trial Registration: ChiCTR-IOR-16007700; www.chictr.org.cn/showprojen.aspx?proj=12972.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244916PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904220PMC
February 2021

Associations of early pregnancy BMI with adverse pregnancy outcomes and infant neurocognitive development.

Sci Rep 2021 Feb 15;11(1):3793. Epub 2021 Feb 15.

College of Life Sciences, University of Leicester, Leicester, UK.

The prevalence of overweight and obesity amongst reproductive women has been increasing worldwide. Our aim was to compare pregnancy outcomes and infant neurocognitive development by different BMI classifications and investigate whether early pregnancy BMI was associated with risks of adverse outcomes in a Southwest Chinese population. We analysed data from 1273 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) randomized controlled trial in Chongqing, China. Maternal BMI was classified as underweight, normal weight and overweight/obese according to the Chinese, WHO Asian, and WHO European standards. For the adverse pregnancy outcomes, after adjustment for potential confounders, an underweight BMI was associated with increased risk of small for gestational age (SGA) babies, and an overweight/obese BMI was associated with increased risk of maternal gestational diabetes mellitus (GDM), caesarean section (C-section), macrosomia and large for gestational age (LGA) babies. For infant neurocognitive development, 1017 mothers and their children participated; no significant differences were seen in the Mental Development Index (MDI) or the Psychomotor Development Index (PDI) between the three BMI groups. Our findings demonstrate that abnormal early pregnancy BMI were associated with increased risks of adverse pregnancy outcomes in Chinese women, while early pregnancy BMI had no significant influence on the infant neurocognitive development at 12 months of age.
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http://dx.doi.org/10.1038/s41598-021-83430-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884778PMC
February 2021

Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial.

JAMA Netw Open 2020 12 1;3(12):e2030415. Epub 2020 Dec 1.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation.

Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism.

Design, Setting, And Participants: This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020.

Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo.

Main Outcomes And Measures: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition.

Results: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial.

Conclusions And Relevance: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits.

Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.30415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753902PMC
December 2020

Double-blind RCT of fish oil supplementation in pregnancy and lactation to improve the metabolic health in children of mothers with overweight or obesity during pregnancy: study protocol.

BMJ Open 2020 12 15;10(12):e041015. Epub 2020 Dec 15.

Liggins Institute, University of Auckland, Auckland, New Zealand

Introduction: Maternal obesity during pregnancy is associated with adverse changes in body composition and metabolism in the offspring. We hypothesise that supplementation during pregnancy of overweight and obese women may help prevent the development of greater adiposity and metabolic dysfunction in children. Previous clinical trials investigating fish oil supplementation in pregnancy on metabolic outcomes and body composition of the children have not focused on the pregnancies of overweight or obese women.

Methods And Analysis: A double-blind randomised controlled trial of fish oil (providing 3 g/day of n-3 polyunsaturated fatty acids) versus an equal volume of olive oil (control) taken daily from recruitment until birth, and in breastfeeding mothers, further continued for 3 months post partum. Eligible women will have a singleton pregnancy at 12-20 weeks' gestation and be aged 18-40 years with body mass index ≥25 kg/m at baseline. We aim to recruit a minimum of 128 participants to be randomised 1:1. Clinical assessments will be performed at baseline and 30 weeks of pregnancy, including anthropometric measurements, fasting metabolic markers, measures of anxiety, physical activity, quality of life and dietary intake. Subsequent assessments will be performed when the infant is 2 weeks, 3 months and 12 months of age for anthropometry, body composition (dual-energy X-ray absorptiometry (DXA)) and blood sampling. The primary outcome of the study is a between-group difference in infant percentage body fatness, assessed by DXA, at 2 weeks of age. Secondary outcomes will include differences in anthropometric measures at each time point, percentage body fat at 3 and 12 months and homeostatic model assessment of insulin resistance at 3 months. Statistical analysis will be carried out on the principle of intention to treat.

Ethics And Dissemination: This trial was approved by the Northern A Health and Disabilities Ethics Committee, New Zealand Ministry of Health (17/NTA/154). Results will be published in a peer-reviewed journal.

Trial Registration Number: ACTRN12617001078347p; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-041015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745511PMC
December 2020

High prevalence of undiagnosed comorbidities among adolescents with obesity.

Sci Rep 2020 11 18;10(1):20101. Epub 2020 Nov 18.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Metabolic diseases are increasing among adolescents with obesity. Although the reported prevalence of metabolic syndrome is approximately 30% worldwide, its prevalence is largely unknown among New Zealand adolescents. Therefore, we assessed the health of adolescents with obesity (BMI ≥ 30 kg/m) enrolled in a randomised clinical trial (Gut Bugs Trial), to identify the prevalence of undiagnosed comorbidities. Assessments included anthropometry, 24-h ambulatory blood pressure monitoring, and insulin sensitivity. We report on baseline data (pre-randomisation) on 87 participants (14-18 years; 59% females), with mean BMI 36.9 ± 5.3 kg/m (BMI SDS 3.33 ± 0.79). Approximately 40% of participants had undiagnosed metabolic syndrome, which was twice as common among males. Half (53%) had pre-diabetes and 92% a reduction in insulin sensitivity. Moreover, 31% had pre-hypertension/hypertension, 69% dyslipidaemia, and 25% abnormal liver function. Participants with class III obesity had a greater risk of metabolic syndrome than those with classes I/II [relative risk 1.99 (95% CI 1.19, 3.34)]. Risks for pre-hypertension/hypertension and inflammation were also greater among those with class III obesity. We identified a high prevalence of undiagnosed comorbidities among adolescents with obesity in New Zealand. As adolescent obesity tracks into adulthood, early interventions are needed to prevent progression to overt cardiometabolic diseases.
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http://dx.doi.org/10.1038/s41598-020-76921-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674474PMC
November 2020

Birth Size and Rapid Infant Weight Gain-Where Does the Obesity Risk Lie?

J Pediatr 2021 Mar 4;230:238-243. Epub 2020 Nov 4.

Liggins Institute, The University of Aucklan, Auckland, New Zealand; A Better Start - National Science Challenge, Auckland, New Zealand. Electronic address:

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http://dx.doi.org/10.1016/j.jpeds.2020.10.078DOI Listing
March 2021

Omega-3 fats in pregnancy: could a targeted approach lead to better metabolic health for children?

Nutr Rev 2021 Apr;79(5):574-584

Liggins Institute, University of Auckland, Auckland, New Zealand.

The prevalence of childhood obesity is increasing worldwide, and the children of women who are obese during pregnancy are at greatest risk. This risk may be mediated by exaggeration of the normal insulin resistance of pregnancy. Omega-3 (n-3) fats are insulin sensitizing. Supplementation during pregnancy may reduce metabolic risk and adiposity in the children. Though results from animal studies are encouraging, completed clinical trials have not demonstrated this benefit. However, to our knowledge, previous studies have not targeted women who are overweight or obese while pregnant-the group at greatest risk for insulin resistance and most likely to benefit from n-3. In this narrative review, the importance of performing clinical trials restricted to women who are overweight or obese is discussed, as is the potential importance of n-3 dose, oil source and quality, and the timing of the intervention.
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http://dx.doi.org/10.1093/nutrit/nuaa071DOI Listing
April 2021

Fundamentals of Data Collection in Clinical Studies: Simple Steps to Avoid "Garbage In, Garbage Out".

Int J Low Extrem Wounds 2020 Jul 31:1534734620938234. Epub 2020 Jul 31.

NCD Center of Excellence, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.

Many fundamental steps underpin the delivery of high-quality clinical research. In this article, we provide a brief commentary on some important aspects associated with the collection and management of data during clinical studies, which, if overlooked, will lead to poor-quality research. In particular, we discuss the key aspects that should help early career researchers maximize the relevance and impact of their clinical research.
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http://dx.doi.org/10.1177/1534734620938234DOI Listing
July 2020

Robotic automation of a UHPLC/MS-MS method profiling one-carbon metabolites, amino acids, and precursors in plasma.

Anal Biochem 2020 03 3;592:113558. Epub 2020 Jan 3.

Liggins Institute, The University of Auckland, New Zealand; New Zealand National Science Challenge "High-Value Nutrition", New Zealand.

Amino acids (AAs) and one-carbon (1-C) metabolism compounds are involved in a range of key metabolic pathways, and mediate numerous health and disease processes in the human body. Previous assays have quantified a limited selection of these compounds and typically require extensive manual handling. Here, we describe the robotic automation of an analytical method for the simultaneous quantification of 37 1-C metabolites, amino acids, and precursors using reversed-phase ultra-high-pressure liquid chromatography coupled with tandem mass spectrometry (UHPLC/MS-MS). Compound extraction from human plasma was tested manually before being robotically automated. The final automated analytical panel was validated on human plasma samples. Our automated and multiplexed method holds promise for application to large cohort studies.
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http://dx.doi.org/10.1016/j.ab.2019.113558DOI Listing
March 2020

Partial remission in type 1 diabetes and associated factors: Analysis based on the insulin dose-adjusted hemoglobin A1c in children and adolescents from a regional diabetes center, Auckland, New Zealand.

Pediatr Diabetes 2019 11 4;20(7):892-900. Epub 2019 Jul 4.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Background: Partial remission (PREM) by the insulin dose-adjusted HbA1c (IDAA1c) method has not been evaluated for the combined associations of ethnicity and socioeconomic status in children and adolescents with type 1 diabetes (T1D).

Objective: To investigate prevalence and predictors of PREM defined by IDAA1c.

Methods: Six hundred fourteen of 678 children (aged <15 years) with new-onset T1D (2000-2013) from a regional pediatric diabetes service (Auckland, New Zealand).

Results: Overall rate of PREM at 3 months was 42.4%, and lower in Māori/Pacific children (28.6%; P = .006) and those of other ethnicities (28.8%; P = .030) compared with New Zealand Europeans (50.4%). Comparing the most and least deprived socioeconomic quintiles, the odds of PREM were lower among the most deprived (adjusted odds ratio [aOR] 0.44; P = .019). Lower rates of PREM were seen in children aged 0 to 4.9 years (23.8%) and 10 to 14 years (40.9%) than in children aged 5 to 9.9 years (57.4%; P < .05). Further predictors of lower rates of PREM were ketoacidosis at diagnosis (aOR 0.54 with DKA; P = .002) and diabetes duration (aOR 0.84 per month; P < .0001). Patient's sex, body mass index standard deviation score, or autoantibodies were not associated with PREM. PREM at 3 months was associated with lower HbA1c over 18 months compared with children not in PREM (65.0 vs 71.3 mmol/mol; P < .0001), independent of ketoacidosis.

Conclusions: This study on a regional cohort of youth with T1D showed social and ethnic disparities in rates of PREM defined by IDAA1c. Further research into reducing ketoacidosis rates at diagnosis and addressing factors associated with lower rates of PREM in non-European children are important health priorities.
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http://dx.doi.org/10.1111/pedi.12881DOI Listing
November 2019

Protocol for the Gut Bugs Trial: a randomised double-blind placebo-controlled trial of gut microbiome transfer for the treatment of obesity in adolescents.

BMJ Open 2019 04 20;9(4):e026174. Epub 2019 Apr 20.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Introduction: Animal studies showed that germ-free mice inoculated with normal mouse gut bacteria developed obesity, insulin resistance and higher triglyceride levels, despite similar food intake. In humans, an association has been found between obesity and gut microbiome dysbiosis. However, gut microbiome transfer has not been evaluated for the treatment of human obesity. We will examine the effectiveness of gut microbiome transfer using encapsulated material for the treatment of obesity in adolescents.

Methods And Analysis: A two-arm, double-blind, placebo-controlled, randomised clinical trial of a single course of gut microbiome transfer will be conducted in 80 obese [body mass index (BMI) ≥30 kg/m] adolescents (males and females, aged 14-18 years) in Auckland, New Zealand. Healthy lean donors (males and females, aged 18-28 years) will provide fresh stool samples from which bacteria will be isolated and double encapsulated. Participants (recipients) will be randomised at 1:1 to control (placebo) or treatment (gut microbiome transfer), stratified by sex. Recipients will receive 28 capsules over two consecutive mornings (~14 mL of frozen microbial suspension or saline). Clinical assessments will be performed at baseline, 6, 12 and 26 weeks, and will include: anthropometry, blood pressure, fasting metabolic markers, dietary intake, physical activity levels and health-related quality of life. Insulin sensitivity (Matsuda index), gut microbiota population structure characterised by 16S rRNA amplicon sequencing and body composition (using dual-energy X-ray absorptiometry) will be assessed at baseline, 6, 12 and 26 weeks. 24-hour ambulatory blood pressure monitoring will be performed at baseline and at 6 weeks. The primary outcome is BMI SD scores (SDS) at 6 weeks, with BMI SDS at 12 and 26 weeks as secondary outcomes. Other secondary outcomes include insulin sensitivity, adiposity (total body fat percentage) and gut microbial composition at 6, 12 and 26 weeks. Statistical analysis will be performed on the principle of intention to treat.

Ethics And Dissemination: Ethics approval was provided by the Northern A Health and Disability Ethics Committee (Ministry of Health, New Zealand; 16/NTA/172). The trial results will be published in peer-reviewed journals and presented at international conferences.

Trial Registration Number: ACTRN12615001351505; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2018-026174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500264PMC
April 2019

Growth Hormone Treatment for Idiopathic Short Stature.

Pediatr Endocrinol Rev 2018 Sep;16(Suppl 1):113-122

Maurice Paykel Research fellow in Paediatric Endocrinology, Liggins Institute, University of Auckland, New Zealand.

ISS is the commonest cause of short stature and poor growth and is arbitrarily defined as a height < -2 SDS without an identified cause. ISS consists largely of normal children with the remainder unrecognised conditions, mainly syndromes and genetic (monogenic and polygenic) causes. Growth response to rhGH is widely variable reflecting the heterogeneity of ISS. Further identification of genetic causes of ISS will better characterise treatment response. rhGH during childhood has been shown in RCTs to improve adult height by approximately 4 cm which is less than seen in other treated growth disorders. Factors that influence response include; younger age, longer birth length, lower height compared to mid-parental height, delayed bone age and larger rhGH dose. The evidence that short stature is associated with psychological well-being and quality of life is minimal and that rhGH could improve this is scant. Further research in this area is urgently required.
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http://dx.doi.org/10.17458/per.vol16.2018.ca.ghidiopathicshortstatureDOI Listing
September 2018

Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor.

Endocrinol Diabetes Metab Case Rep 2018 23;2018. Epub 2018 Aug 23.

Starship Children's Health, Auckland District Health Board, Auckland, New Zealand.

Adrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In addition to the anticipated side effect of adrenal insufficiency, mitotane is known to cause gynecomastia and hypothyroidism in adults. It has never been reported to cause precocious puberty. A 4-year-old girl presented with a 6-week history of virilization and elevated androgen levels and 1-year advancement in bone age. Imaging revealed a right adrenal mass, which was subsequently surgically excised. Histology revealed ACC with multiple unfavorable features, including high mitotic index, capsular invasion and atypical mitoses. Adjuvant chemotherapy was started with mitotane, cisplatin, etoposide and doxorubicin. She experienced severe gastrointestinal side effects and symptomatic adrenal insufficiency, which occurred despite physiological-dose corticosteroid replacement. She also developed hypothyroidism that responded to treatment with levothyroxine and peripheral precocious puberty (PPP) with progressive breast development and rapidly advancing bone age. Five months after discontinuing mitotane, her adrenal insufficiency persisted and she developed secondary central precocious puberty (CPP). This case demonstrates the diverse endocrine complications associated with mitotane therapy, which contrast with the presentation of ACC itself. It also provides the first evidence that the known estrogenic effect of mitotane can manifest as PPP.

Learning Points: Adrenocortical carcinoma is an important differential diagnosis for virilization in young childrenMitotane is a chemotherapeutic agent that is used to treat adrenocortical carcinoma and causes adrenal necrosisMitotane is an endocrine disruptor. In addition to the intended effect of adrenal insufficiency, it can cause hypothyroidism, with gynecomastia also reported in adults.Patients taking mitotane require very high doses of hydrocortisone replacement therapy because mitotane interferes with steroid metabolism. This effect persists after mitotane therapy is completedIn our case, mitotane caused peripheral precocious puberty, possibly through its estrogenic effect.
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http://dx.doi.org/10.1530/EDM-18-0059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109212PMC
August 2018

Socioeconomic status is not associated with health-related quality of life in a group of overweight middle-aged men.

PeerJ 2018 13;6:e5193. Epub 2018 Jul 13.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Socioeconomic status is a known determinant of health. In secondary data analyses, we assessed whether socioeconomic status affected health-related quality of life in a group of overweight (body mass index 25-30 kg/m) middle-aged (45.9 ± 5.4 years) men, recruited in Auckland (New Zealand). Health-related quality of life was assessed with SF-36v2 three times: at baseline, and 12 and 30 weeks later. Socioeconomic status was determined by geo-coded deprivation scores derived from current address using the New Zealand Index of Deprivation 2006 (NZDep2006), as well as capital value of residence. Univariable and multivariable analyses showed no associations between measures of socioeconomic status and any mental or physical health domains. Our findings may reflect the fact that these men are not currently experiencing comorbidities associated with overweight.
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http://dx.doi.org/10.7717/peerj.5193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047501PMC
July 2018

A Weighty Matter: Can PUFAs in Pregnancy Prevent Obesity?

Diabetes 2018 04;67(4):548-549

Liggins Institute, University of Auckland, and A Better Start National Science Challenge, Auckland, New Zealand

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http://dx.doi.org/10.2337/dbi17-0051DOI Listing
April 2018

Insulin regimens for newly diagnosed children with type 1 diabetes mellitus in Australia and New Zealand: A survey of current practice.

J Paediatr Child Health 2017 Dec 20;53(12):1208-1214. Epub 2017 Jul 20.

Department of Women's and Children's Health, University of Otago, Dunedin, New Zealand.

Aim: There is no consensus on the optimal insulin treatment for children newly diagnosed with type 1 diabetes mellitus (T1DM). The aims of this study were (i) to describe the insulin regimens used at diagnosis by patient age and geographical region and (ii) to explore differences between and within Australia (AU) and New Zealand (NZ) with regards to other aspects of patient management and education.

Methods: An online survey of medical professionals caring for children with T1DM in AU and NZ was undertaken. Questions included clinic demographics, insulin regimen/dosing choices and patient education.

Results: Of 110 clinicians identified, 100 responded (91%). The majority of those in AU (69%, P < 0.0001) favour multiple daily injections (MDI) for all ages. In NZ, for patients < 10 years old, (twice daily (BD)) BD therapy was favoured (75%, P < 0.0001), with MDI dominant for ages ≥ 10 years (82%, P < 0.0001). Insulin pump therapy was never considered at diagnosis in NZ, but 38% of clinicians in AU considered using pumps at diagnosis in patients <2 years, but rarely in patients aged 2 and over (16%). Differences in clinician choices were also seen in relation to starting insulin dose.

Conclusion: This is the first study to examine current clinical practice with regards to children newly diagnosed with T1DM. Practice varies across Australasia by clinician and region. This lack of consensus is likely driven by ongoing debates in the current paediatric diabetes evidence base as well as by differences in clinician/centre preference, variations in resourcing and their interpretations of the influence of various patient factors.
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http://dx.doi.org/10.1111/jpc.13631DOI Listing
December 2017

Fish oil supplementation to rats fed high-fat diet during pregnancy prevents development of impaired insulin sensitivity in male adult offspring.

Sci Rep 2017 07 17;7(1):5595. Epub 2017 Jul 17.

Liggins Institute, University of Auckland, Auckland, New Zealand.

We examined whether maternal fish oil supplementation during pregnancy could prevent development of insulin resistance in adult male offspring of rat dams fed a high-fat diet. Time-mated Sprague-Dawley rat dams were randomised into four treatment groups: Con-Con, dams fed a control diet (fat: 15% kcal) and administered water by gavage; Con-FO, control diet with unoxidised fish oil by gavage; HF-Con, high-fat diet (fat: 45% kcal) and water by gavage; and HF-FO, high-fat diet and unoxidised fish oil by gavage. Dams were fed the allocated diet ad libitum during pregnancy and lactation, but daily gavage occurred only during pregnancy. After weaning, male offspring consumed a chow diet ad libitum until adulthood. Maternal high-fat diet led to increased food consumption, adiposity, systolic blood pressure, and triglycerides and plasma leptin in adult HF-Con offspring. HF-Con offspring also exhibited lower insulin sensitivity than Con-Con rats. Male offspring from HF-FO group were similar to HF-Con regarding food consumption and most metabolic parameters. However, insulin sensitivity in the HF-FO group was improved relative to the HF-Con offspring. Supplementation with unoxidised n-3 PUFA rich oils in the setting of a maternal obesogenic diet improved insulin sensitivity, but had no impact on body composition of adult male offspring.
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http://dx.doi.org/10.1038/s41598-017-05793-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514114PMC
July 2017

Reply to "Letter to the Editor: Determining the potential effects of oxidized fish oils in pregnant women requires a more systematic approach".

Am J Physiol Regul Integr Comp Physiol 2017 02 9;312(2):R264. Epub 2017 Feb 9.

Liggins Institute, University of Auckland, Auckland, New Zealand; and

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http://dx.doi.org/10.1152/ajpregu.00531.2016DOI Listing
February 2017

Non-Dipping and Cardiometabolic Profile: A Study on Normotensive Overweight Middle-Aged Men.

Heart Lung Circ 2016 Dec 17;25(12):1218-1225. Epub 2016 May 17.

Liggins Institute, University of Auckland, Auckland, New Zealand; Gravida: National Centre for Growth and Development, Auckland, New Zealand. Electronic address:

Background: We aimed to assess insulin sensitivity and other metabolic features of dippers and non-dippers among overweight middle-aged men.

Methods: We studied 73 men (45.8 ± 5.3 years) who were overweight but normotensive. Participants were separated into dippers and non-dippers based on the magnitude of the nocturnal decline of blood pressure, with dippers experiencing an overnight decline ≥10% as per standard definition. Our study included 51 dippers and 22 non-dippers. All participants underwent 24-hour ambulatory blood pressure monitoring. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test; other assessments included carotid artery intima-media thickness (CIMT), body composition derived from dual-energy X-ray absorptiometry, lipid profiles, and a physical activity questionnaire.

Results: Non-dippers had lower daytime systolic (-5.0mmHg; p=0.022) and diastolic (-3.3mmHg; p=0.035) blood pressure than dippers. Conversely, during sleep, non-dippers had higher systolic (+6.5mmHg; p=0.003) and diastolic (+5.6mmHg; p=0.001) blood pressure. In continuous associations, increasing CIMT was associated with decreasing systolic (p=0.012) and diastolic (p=0.042) dipping. Thus, non-dippers had CIMT that was 9% greater than that of dippers (749 vs 820μm; p=0.036). Importantly, there was no association between non-dipping status or the magnitude of the nocturnal dip with insulin sensitivity.

Conclusions: Non-dippers had lower blood pressure in the daytime, but higher blood pressure in the night time compared to dippers. Non-dippers had increased CIMT, which suggests that normotensive men with a non-dipping ambulatory blood pressure profile may be at increased cardiovascular risk. However, it appears that the non-dipping profile is unrelated to dysfunction of glucose homeostasis in overweight normotensive men.
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http://dx.doi.org/10.1016/j.hlc.2016.04.012DOI Listing
December 2016

Pathways to reduce diabetic ketoacidosis with new onset type 1 diabetes: Evidence from a regional pediatric diabetes center: Auckland, New Zealand, 2010 to 2014.

Pediatr Diabetes 2017 Nov 11;18(7):553-558. Epub 2016 Oct 11.

Starship Children's Hospital, Auckland District Health Board, Auckland, New Zealand.

Background: There has been little change in the incidence of diabetic ketoacidosis (DKA) in newly diagnosed type 1 diabetes mellitus (T1DM) in children and adolescents in most developed countries.

Objectives: To assess potentially modifiable antecedents of DKA in children <15 years of age with new onset T1DM.

Methods: Retrospective review of prospectively collected data from a complete regional cohort of children with T1DM in Auckland (New Zealand) from 2010 to 2014. DKA and severity were defined according to the ISPAD 2014 guidelines.

Results: A total of 263 children presented with new onset T1DM during the 5-year study period at 9.0 years of age (range 1.0-14.7), of whom 61% were NZ-European, 14% Maori, 13% Pacifica, and 11% other. A total of 71 patients (27%) were in DKA, including 31 mild, 20 moderate, and 20 severe DKA. DKA was associated with no family history of T1DM, higher glycated hemoglobin (HbA1c) values at presentation, self-presenting to secondary care, health care professional contacts in the 4 weeks before final presentation, and greater deprivation. Although a delay in referral from primary care for laboratory testing was common (81/216), only delay for more than 48 hours was associated with increased risk of DKA (11/22 > 48 h vs 12/59 referred at <48 h, P = .013).

Conclusions: These data suggest that in addition to lack of family awareness potentially modifiable risk factors for new onset DKA include prolonged delay for laboratory testing and a low index of medical suspicion for T1DM leading to delayed diagnosis.
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http://dx.doi.org/10.1111/pedi.12456DOI Listing
November 2017

Oxidized fish oil in rat pregnancy causes high newborn mortality and increases maternal insulin resistance.

Am J Physiol Regul Integr Comp Physiol 2016 09 6;311(3):R497-504. Epub 2016 Jul 6.

Liggins Institute, University of Auckland, Auckland, New Zealand;

Fish oil is commonly taken by pregnant women, and supplements sold at retail are often oxidized. Using a rat model, we aimed to assess the effects of supplementation with oxidized fish oil during pregnancy in mothers and offspring, focusing on newborn viability and maternal insulin sensitivity. Female rats were allocated to a control or high-fat diet and then mated. These rats were subsequently randomized to receive a daily gavage treatment of 1 ml of unoxidized fish oil, a highly oxidized fish oil, or control (water) throughout pregnancy. At birth, the gavage treatment was stopped, but the same maternal diets were fed ad libitum throughout lactation. Supplementation with oxidized fish oil during pregnancy had a marked adverse effect on newborn survival at day 2, leading to much greater odds of mortality than in the control (odds ratio 8.26) and unoxidized fish oil (odds ratio 13.70) groups. In addition, maternal intake of oxidized fish oil during pregnancy led to increased insulin resistance at the time of weaning (3 wks after exposure) compared with control dams (HOMA-IR 2.64 vs. 1.42; P = 0.044). These data show that the consumption of oxidized fish oil is harmful in rat pregnancy, with deleterious effects in both mothers and offspring.
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http://dx.doi.org/10.1152/ajpregu.00005.2016DOI Listing
September 2016

Reply to N Hoem.

Am J Clin Nutr 2016 06;103(6):1558-9

From the Liggins Institute, University of Auckland, Auckland, New Zealand (BBA, JGBD, DC-S, PLH; WSC, e-mail: and the Nutraceuticals Research Group, University of Newcastle, Callaghan, Australia (MLG).

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http://dx.doi.org/10.3945/ajcn.116.133785DOI Listing
June 2016

Fishing for answers: is oxidation of fish oil supplements a problem?

J Nutr Sci 2015 23;4:e36. Epub 2015 Nov 23.

Liggins Institute , University of Auckland , Auckland , New Zealand.

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http://dx.doi.org/10.1017/jns.2015.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681158PMC
December 2015

Proposed changes to the Pharmacy Council of New Zealand Code of Ethics would undermine the trusted position of pharmacists in the delivery of science based health care.

N Z Med J 2015 Oct 16;128(1423):86-8. Epub 2015 Oct 16.

Paediatric Endocrinologist, Liggins Institute, University of Auckland, Auckland.

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October 2015

Supplementation with a blend of krill and salmon oil is associated with increased metabolic risk in overweight men.

Am J Clin Nutr 2015 Jul 27;102(1):49-57. Epub 2015 May 27.

Liggins Institute, University of Auckland, Auckland, New Zealand; and

Background: Krill is an increasingly popular source of marine n-3 (ω-3) PUFA that is seen as a premium product. However, to our knowledge, the effect of krill-oil supplementation on insulin sensitivity in humans has not been reported.

Objective: We assessed whether supplementation with a blend of krill and salmon (KS) oil [which is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] affects insulin sensitivity in overweight men.

Design: The design was a randomized, double-blind, controlled crossover trial. A total of 47 men with a mean ± SD age of 46.5 ± 5.1 y, who were overweight [body mass index (in kg/m(2)) from 25 to 30] but otherwise healthy, received 5 1-g capsules of KS oil or a control (canola oil) for 8 wk and crossed over to another treatment after an 8-wk washout period. The primary outcome was insulin sensitivity assessed by using the Matsuda method from an oral-glucose-tolerance test. Secondary outcomes included lipid profiles, inflammatory markers, 24-h ambulatory blood pressure, and carotid artery intimamedia thickness.

Results: Unexpectedly, insulin sensitivity (per the Matsuda index) was 14% lower with the KS oil than with the control oil (P = 0.049). A mediation analysis showed that, after controlling for the likely positive effects of blood EPA and DHA (i.e., the omega-3 index), the reduction in insulin sensitivity after KS-oil supplementation was more marked [27% lower than with the control oil (P = 0.009)].

Conclusions: Supplementation with a blend of KS oil is associated with decreased insulin sensitivity. Thus, krill-oil supplementation in overweight adults could exacerbate risk of diabetes and cardiovascular disease. This trial was prospectively registered at the Australian New Zealand Clinical Trials Registry as ACTRN12611000602921.
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http://dx.doi.org/10.3945/ajcn.114.103028DOI Listing
July 2015

15-year incidence of diabetic ketoacidosis at onset of type 1 diabetes in children from a regional setting (Auckland, New Zealand).

Sci Rep 2015 May 19;5:10358. Epub 2015 May 19.

1] Liggins Institute, University of Auckland, Auckland, New Zealand [2] Gravida: National Centre for Growth and Development, Auckland, New Zealand.

We assessed the incidence of diabetic ketoacidosis (DKA) in children aged <15 years with newly diagnosed type 1 diabetes mellitus (T1DM) in the Auckland Region (New Zealand) in 1999-2013, in a retrospective review of a complete regional cohort. DKA and its severity were classified according to ISPAD 2014 guidelines. Of 730 children presenting with new-onset T1DM over the 15-year time period, 195 cases had DKA of any severity (27%). There was no change in the incidence of DKA or the proportion of children with severe DKA at presentation. The incidence of DKA among children aged <2.0 years (n = 40) was 53% compared to 25% for those aged 2-14 years (n = 690; p = 0.005). In children aged 2-14 years, increasing age at diagnosis was associated with greater likelihood of DKA at presentation (p = 0.025), with the odds of DKA increasing 1.06 times with each year increase in age. Non-Europeans were more likely to present in DKA than New Zealand Europeans (OR 1.52; p = 0.048). Despite a consistent secular trend of increasing incidence of T1DM, there was no reduction in the incidence of DKA in new-onset T1DM in the Auckland Region over time. Thus, it is important to explore ways to reduce DKA risk.
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http://dx.doi.org/10.1038/srep10358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650806PMC
May 2015

Fish oil supplements in New Zealand are highly oxidised and do not meet label content of n-3 PUFA.

Sci Rep 2015 Jan 21;5:7928. Epub 2015 Jan 21.

Liggins Institute, University of Auckland, Auckland, New Zealand.

We evaluated the quality and content of fish oil supplements in New Zealand. All encapsulated fish oil supplements marketed in New Zealand were eligible for inclusion. Fatty acid content was measured by gas chromatography. Peroxide values (PV) and anisidine values (AV) were measured, and total oxidation values (Totox) calculated. Only 3 of 32 fish oil supplements contained quantities of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that were equal or higher than labelled content, with most products tested (69%) containing <67%. The vast majority of supplements exceeded recommended levels of oxidation markers. 83% products exceeded the recommended PV levels, 25% exceeded AV thresholds, and 50% exceeded recommended Totox levels. Only 8% met the international recommendations, not exceeding any of these indices. Almost all fish oil supplements available in the New Zealand market contain concentrations of EPA and DHA considerably lower than claimed by labels. Importantly, the majority of supplements tested exceeded the recommended indices of oxidative markers. Surprisingly, best-before date, cost, country of origin, and exclusivity were all poor markers of supplement quality.
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http://dx.doi.org/10.1038/srep07928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300506PMC
January 2015

Increasing parental age at childbirth is associated with greater insulin sensitivity and more favorable metabolic profile in overweight adult male offspring.

Am J Hum Biol 2015 May-Jun;27(3):380-6. Epub 2014 Nov 13.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Objective: To assess the effect of parental age at childbirth on insulin sensitivity and other metabolic outcomes in overweight middle-aged males.

Methods: We studied 73 men aged 46.0±5.4 years, who were overweight (body mass index, BMI 25-30 kg/m(2) ) but otherwise healthy. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test. Other assessments included dual-energy X-ray absorptiometry-derived body composition, lipid profile, 24-hour ambulatory blood pressure, and carotid intima-media thickness. Maternal and paternal ages were highly correlated (r = 0.71; P < 0.0001), and the main parameter of interest in this study was the mean parental age at childbirth (MPAC), calculated as the average of maternal and paternal ages.

Results: Increasing MPAC was associated with a continuous increase in insulin sensitivity (β = 0.193; P = 0.008), as well as reductions in insulin resistance (HOMA-IR; β = -0.064; P = 0.011), fasting insulin (β = -0.221; P = 0.018) and fasting glucose (β = -0.030; P = 0.033) concentrations. Increasing MPAC was also associated with reductions in night time systolic (β = -0.500; P = 0.020) and diastolic (β = -0.325; P = 0.047) blood pressure, as well as with improved (greater) nocturnal diastolic blood pressure dipping (β = 0.413; P = 0.046). Subgroup analyses on participants of European descent (n = 64) showed that increasing MPAC was associated with reduced carotid intima-media thickness (β = -0.008; P = 0.018) and lower low-density lipoprotein cholesterol concentrations (β = -0.042; P = 0.028).

Conclusions: Increasing parental age at childbirth was associated with a more favorable metabolic phenotype in overweight middle-aged males. However, it is unknown whether the effect was maternal, paternal, or both. Future studies on the effects of parental age at childbirth on the metabolism of males and females across the BMI range are required.
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http://dx.doi.org/10.1002/ajhb.22654DOI Listing
January 2016