Combining mussel with fucoidan as a supplement for joint pain and prediabetes: Study protocol for a randomized, double-blinded, placebo-controlled trial.

Introduction: Pharmaceutical drugs are beneficial to inflammatory conditions but with side effects, which led to the search for alternative therapies. Perna canaliculus, the New Zealand green-lipped mussel, have shown promise in placebo-controlled trials for inflammatory conditions. Fucoidan, an extract from seaweed Undaria pinnatifida, has been found to have beneficial effects on joint pain and insulin resistance. However, green-lipped mussel and fucoidan have never been combined. Methods and analysis: A parallel, two-arm, double-blind, randomized, placebo-controlled trial will be conducted in New Zealand to determine whether a food product supplemented with green-lipped mussel and fucoidan improves joint pain and/or insulin resistance. Those who are ethnically Chinese, are aged over 30 years, have prediabetes and hip or knee joint pain will be eligible to participate. They will be randomized at 1:1 ratio to consume either dark chocolate supplemented with 1000 mg mussel powder and 1000 mg fucoidan or dark chocolate with no active substances daily for 100 days. The primary endpoints are change in insulin resistance and patient-reported joint pain. Secondary endpoints include anthropometry, fasting glucose and insulin, HbA1c, inflammatory markers, satiety, quality of life, physical function, pain intensity, and analgesic medication use. A sample size of 150 (75 per arm) will provide 90% power at an overall significance level of 5% (two-sided) to detect a standardized effect size of 0.625 on either of the two co-primary outcomes allowing for 10% loss. Ethics and dissemination: The study was approved by the Health and Disability Ethics Committee (number: 20/STH/153). Results will be made available to participants, funders, and other researchers. Discussion: This trial will provide data on the potential utility of a mussel-fucoidan supplement in reducing joint pain and/or insulin resistance, to inform the development of a supplemented food product suitable for the Chinese market. Clinical trial registration: https://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12621000413820, ANZCTR Registration: ACTRN12621000413820, on 15 April 2021.

Effect of Lactobacillus rhamnosus Probiotic in Early Pregnancy on Plasma Conjugated Bile Acids in a Randomised Controlled Trial.

We have previously shown that probiotic supplementation with Lactobacillus rhamnosus HN001 (HN001) led to a reduced incidence of gestational diabetes mellitus (GDM). Here we investigate whether HN001 supplementation resulted in alterations in fasting lipids, insulin resistance, or bile acids (BAs) during pregnancy. Fasting plasma samples collected at 24-30 weeks' gestation, from 348 women randomised at 14-16 weeks' gestation to consume daily probiotic HN001 (n = 172) or a placebo (n = 176) were analysed for lipids, insulin, glucose and BAs. Women supplemented with HN001 had lower fasting glucose compared with placebo (p = 0.040), and lower GDM. Significant differences were found in fasting insulin, HOMA-IR, low density lipoprotein-cholesterol (LDL-c), high density lipoprotein (HDL)-c, triglycerides, total cholesterol, and BAs by GDM status. Lower fasting conjugated BAs were seen in women receiving HN001. A significant decrease of glycocholic acid (GCA) was found in older (age ≥ 35) women who received HN001 (p = 0.005), while GDM women showed significant reduced taurodeoxycholic acid (TDCA) (p = 0.018). Fasting conjugated BA was positively correlated with fasting glucose (r = 0.136, p = 0.020) and fasting insulin (r = 0.113, p = 0.036). Probiotic HN001 supplementation decreases conjugated BAs and might play a role in the improvement of glucose metabolism in women with pregnancy.

Effect of antenatal dietary interventions in maternal obesity on pregnancy weight-gain and birthweight: Healthy Mums and Babies (HUMBA) randomized trial.

BACKGROUND: Pregnancy interventions that improve maternal and infant outcomes are urgently needed in populations with high rates of obesity. We undertook the Healthy Mums and Babies (HUMBA) randomized controlled trial to assess the effect of dietary interventions and or probiotics in a multiethnic population of pregnant women with obesity, living in an area of high deprivation. OBJECTIVES: To determine whether a culturally tailored dietary intervention and or daily probiotic capsules in pregnant women with obesity reduces the co-primary outcomes of (1) excessive gestational weight gain (mean >0.27 kg/week) and (2) birthweight. STUDY DESIGN: We conducted a 2 × 2 factorial, randomized controlled trial in women without diabetes at pregnancy booking, body mass index ≥30 kg/m2, and a singleton pregnancy. At 12+0 to 17+6 weeks' gestation, eligible women were randomized to a dietary intervention (4 tailored educational sessions at ≤28 weeks' gestation by a community health worker trained in key aspects of pregnancy nutrition plus text messaging until birth) or to routine dietary advice; and to daily capsules containing either (Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12, minimum 6.5 × 109 colony forming units), or placebo, until birth. Analysis was by intention to treat with adjustment for maternal baseline body mass index. Infant outcomes were additionally adjusted for ethnicity, sex, and gestational age at birth. RESULTS: In total, 230 women were recruited between April 2015 and June 2017 (dietary intervention N = 116 vs routine dietary advice N = 114; probiotics N = 115 vs placebo N = 115). Baseline characteristics and demographic variables were similar across all groups. There was no significant difference between intervention groups, for the co-primary outcomes of (1) proportion of women with excessive gestational weight gain (dietary intervention vs routine advice: 79/107 [73.8%] vs 90/110 [81.8%], adjusted relative risk [relative risk, 0.92; 95% confidence interval, 0.80-1.05]; probiotics versus placebo: 89/108 [82.4%] and 80/109 [73.4%], relative risk, 1.14, 95% confidence interval, 0.99-1.31) or (2) birthweight (dietary intervention vs routine advice: 3575 vs 3612 g, adjusted mean difference, -24 g, 95% confidence interval, -146 to 97; probiotics vs placebo: 3685 vs 3504 g, adjusted mean difference, 107 g, 95% confidence interval, -14 to 228). Total maternal weight gain, a secondary outcome, was lower with dietary intervention compared with routine dietary advice (9.7 vs 11.4 kg, adjusted mean difference, -1.76, 95% confidence interval, -3.55 to 0.03). There were no significant differences between intervention groups in other secondary maternal or neonatal outcomes. CONCLUSION: Although dietary education and or probiotics did not alter rates of excessive gestational weight gain or birthweight in this multiethnic, high-deprivation population of pregnant women with obesity, dietary education was associated with a modest reduction in total weight gain with potential future benefit for the health of mothers and their offspring if sustained.

Pancreas volume in health and disease: a systematic review and meta-analysis.

INTRODUCTION: The pancreas plays a central role in metabolism and is involved in the pathogenesis of several diseases. Pancreas volume is a holistic quantitative measure of pancreas size but the clinical relevance of pancreas volumetry is poorly understood. Areas covered: The aim was to systematically review studies in adults that used computed tomography or magnetic resonance imaging to measure pancreas volume in health and disease, to determine normal pancreas volume range, and to quantify changes in pancreas volume that are associated with disease. Expert commentary: The normal pancreas volume range in adults is 71-83 cm3, with no statistically significant difference between men and women. Type 2 diabetes and type 1 diabetes are associated with a progressively reduced pancreas volume. Overweight and obesity are associated with a progressively increased pancreas volume. There is a paucity of studies on pancreas volume in the setting of diseases of the exocrine pancreas, which should become a research priority in the future.

Maternal supplementation alone with Lactobacillus rhamnosus HN001 during pregnancy and breastfeeding does not reduce infant eczema.

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-ß/IgA profiles were unchanged. CONCLUSION: Maternal probiotic supplementation without infant supplementation may not be effective for preventing infant eczema.

The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy.

BACKGROUND: Worldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes. The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum. METHODS/DESIGN: The PiP Study is a two-centre, randomised, double-blind placebo-controlled trial in Wellington and Auckland, New Zealand. Four hundred pregnant women expecting infants at high risk of allergic disease will be enrolled in the study at 14-16 weeks gestation and randomised to receive either Lactobacillus rhamnosus HN001 (6 × 10(9) colony-forming units per day (cfu/day)) or placebo until delivery and then continuing until 6 months post-partum, if breastfeeding. Primary infant outcomes are the development and severity of eczema and atopic sensitisation in the first year of life. Secondary outcomes are diagnosis of maternal gestational diabetes mellitus, presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus (at 35-37 weeks gestation). Other outcome measures include maternal weight gain, maternal postpartum depression and anxiety, infant birth weight, preterm birth, and rate of caesarean sections. A range of samples including maternal and infant faecal samples, maternal blood samples, cord blood and infant cord tissue samples, breast milk, infant skin swabs and infant buccal swabs will be collected for the investigation of the mechanisms of probiotic action. DISCUSSION: The study will investigate if mother-only supplementation with Lactobacillus rhamnosus HN001 in pregnancy and while breastfeeding can reduce rates of eczema and atopic sensitisation in infants by 1 year, and reduce maternal rates of gestational diabetes mellitus, bacterial vaginosis, vaginal carriage of Group B Streptococcus before birth and maternal depression and anxiety postpartum. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registration: ACTRN12612000196842. Date Registered: 15/02/12.

Personalized hypertension management in practice.

The revolution occurring in genomic and personalized medicine is likely to have a significant impact on the management of hypertension. However, from the perspective of translating new knowledge into clinical practice, progress has been slow. This review article summarizes recent advances in hypertension-related diagnostics while also offering new perspective on hypertension management for the future. Such new perspectives will likely require a paradigm shift toward more integrated and holistic approaches for better prevention and treatment of hypertension in both individuals and the population as a whole.

Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes.

Monogenic diabetes resulting from mutations that primarily reduce beta-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-1alpha (hepatocyte nuclear factor 1-alpha) or HNF-4alpha, and can be treated with low-dose sulfonylureas. Finally, extrapancreatic features, such as renal disease (caused by mutations in HNF-1beta) or deafness (caused by a mitochondrial m.3243A>G mutation), usually require early treatment with insulin.