Chrono-medicine considers circadian biology in disease management, including combined lifestyle and medicine interventions. Exercise and nutritional interventions are well-known for their efficacy in managing Type 2 Diabetes, and metformin remains a widely used pharmacological agent. However, metformin may reduce exercise capacity and interfere with skeletal muscle adaptations, creating barriers to exercise adherence. Research into optimising the timing of exercise has shown promise, particularly for glycaemic management in people with Type 2 Diabetes. Aligning exercise timing with circadian rhythms and nutritional intake may maximise benefits. Nutritional timing also plays a crucial role in glycaemic control. Recent research suggests that not only what we eat but when we eat significantly impacts glycaemic control, with strategies like time-restricted feeding (TRF) showing promise in reducing caloric intake, improving glycaemic regulation, and enhancing overall metabolic health. These findings suggest that meal timing could be an important adjunct to traditional dietary and exercise approaches in managing diabetes and related metabolic disorders. When taking a holistic view of Diabetes management and the diurnal environment, one must also consider the circadian biology of medicines. Metformin has a circadian profile in plasma, and our recent study suggests that morning exercise combined with pre-breakfast metformin intake reduces glycaemia more effectively than post-breakfast intake. In this review, we aim to explore the integration of circadian biology into Type 2 Diabetes management by examining the timing of exercise, nutrition, and medication. In conclusion, chrono-medicine offers a promising, cost-effective strategy for managing Type 2 Diabetes. Integrating precision timing of exercise, nutrition, and medication into treatment plans requires considering the entire diurnal environment, including lifestyle and occupational factors, to develop comprehensive, evidence-based healthcare strategies.

The popularity of a vegan diet is growing worldwide. Data analysed from the 2018 NZ Attitudes and Values study showed that 1.1% of New Zealanders followed a vegan diet(1). Though there are potential nutrient deficiencies in a vegan diet, it is generally accepted that a vegan diet, with its emphasis on a variety of vegetables, fruit, grains, legumes, and pulses, has greater metabolic benefits than a Western-style diet high in red meat and processed foods and lower in plants(2). This observational cross-sectional study aimed to explore the dietary intake (4-day food diary) and metabolic health status (including anthropometry, blood pressure, lipids, body fat percentage, omega-3 index and glycaemic control) of adults who had been consuming a vegan diet for 2+ years. Participants (N = 212) were predominantly female (N = 155) with a mean (SD) age of 39.5 (12.4) years. Mean cardiometabolic markers of systolic and diastolic blood pressure, BMI, waist circumference, HbA1c, total cholesterol, LDL-cholesterol, HDL-cholesterol, Chol:HDL ratio and triglycerides were all below the thresholds for disease risk. Omega-3 index results <4% placed most participants (86.3%) in the high-risk category for heart disease. Many female participants (71%) had >30% body fat, compared to 5.3% of males. With reference to the AMDR (total fat 20-35%, carbohydrate 45-65% and protein 15-25%), the intake of total fat was at the upper end (males 34.4%, females 35.9%), carbohydrate was at the lower end (males 46.2%, females 44.7%), and protein was below the lower end (males 14.9%, females 14.2%). Saturated fat intakes ranged from 4.0-65.9 g/d, with a mean (SD) of 24.9 (10.5) g/d for males and 20.2 (9.9) g/d for females. The mean (SD) dietary fibre intake was much higher than the AI set by the Ministry of Health of 25g/d for females and 30g/d for males, at 55.0 (17.8) g/d for males and 43.4 (12.8) g/d for females, ranging from 10.9-133.9g/d. This is the first New Zealand study to examine the metabolic health and dietary intake of adult vegans. The results of cardiometabolic health markers indicate that the vegan diet confers cardioprotective benefits. However, the low Omega-3 index of most participants is concerning, which warrants longitudinal research to assess the level of risk conferred by a low Omega-3 index result in a population with no other cardiometabolic risk factors. The findings of the present study may help guide the growing New Zealand vegan community towards a nutritionally optimal vegan diet.

There is significant evidence that an unhealthy diet greatly increases the risk of complications during pregnancy and predisposes offspring to metabolic dysfunction and obesity. While fat intake is typically associated with the onset of obesity and its comorbidities, there is increasing evidence linking sugar, particularly high fructose corn syrup, to the global rise in obesity rates. Furthermore, the detrimental effects of added sugar intake during pregnancy on mother and child have been clearly outlined. Guidelines advising pregnant women to avoid food and beverages with high fat and sugar have led to an increase in consumption of ‘diet’ or ‘light’ options. Examination of some human birth cohort studies shows that heavy consumption (at least one beverage a day) of non-nutritive sweetener (NNS) containing beverages has been associated with increased risk of preterm birth and increased weight/BMI in male offspring independent of maternal weight, which appears to be offset by breastfeeding for 6 months. Rodent models have shown that NNS exposure during pregnancy can impact maternal metabolic health, adipose tissue function, gut microbiome profiles and taste preference. However, the mechanisms underlying these effects are multifaceted and further research, particularly in a translational setting is required to fully understand the effects of NNS on maternal and infant health during pregnancy. Therefore, this review examines maternal sweetener intakes and their influence on fertility, maternal health outcomes and offspring outcomes in human cohort studies and rodent models.

As rates of obesity, diabetes, and related comorbidities have increased, the consumption of artificial sweeteners (ASs) as sugar substitutes has also risen in popularity as they are perceived as a healthier alternative to sugar sweetened products. However, there is conflicting evidence regarding the impact of AS intake on metabolic and reproductive health. Glucose intolerance during pregnancy due to intake of sugar sweetened foods can result in an increased risk for the development of type 2 diabetes post-pregnancy. However, limited information exists on the impact of AS intake during pregnancy and lactation on the mother’s health in later life. We hypothesised both AS and fructose would impair metabolic health post-partum (PP) following maternal consumption during pregnancy and lactation. Female C57Bl/6 mice received a standard control diet ad libitum with either water (CD), fructose (Fr; 34.7 mm intake), or AS (AS;12.5 mm Acesulfame-K) throughout pregnancy and lactation. Post-weaning, AS and Fr dams were fed the CD diet for the remainder of the experiment. Oral glucose tolerance tests were undertaken 8 weeks PP and dams were humanely killed at 9 weeks PP, with adipose tissue and ovaries collected for analysis. Experimental diets did not influence maternal bodyweight. At 8 weeks PP, increased glucose intolerance was evident in both AS and Fr dams. Adipocyte size was significantly increased in both the AS and Fr groups PP. Further, in the ovary, AS increased expression of genes associated with follicular development and ovulation. Therefore, ASs may not represent beneficial substitutes to fructose during pregnancy, with the potential to increase the risk of T2DM in later life in mothers.

Dietary patterns high in fat contribute to the onset of cardiometabolic disease through the accrual of adipose tissue (AT). Lycopene, a carotenoid shown to exert multiple health benefits, may disrupt these metabolic perturbations. The purpose of the present study was to evaluate AT development and obesity-associated metabolic outcomes in the neonate and weanling offspring of Sprague-Dawley mothers fed a high-fat diet (HFD = 50 % fat) with and without lycopene supplementation. Sprague-Dawley rats consumed either a normal fat diet (NFD; 25 % fat) or HFD throughout gestation. Upon delivery, half of HFD mothers were transitioned to an HFD supplemented with 1 % lycopene (HFDL). At postnatal day 14 (P14), P25, and P35, pups were euthanised, body weight was recorded, and visceral white AT (WAT) and brown AT (BAT) mass were determined. Serum redox status, adipokines, glucose and inflammatory biomarkers were evaluated, as well as BAT mRNA expression of uncoupling protein 1 (UCP1). The HFD was effective in inducing weight gain as evident by significantly greater BW and WAT in the HFD group compared to the NFD group across all time points. Compared to HFD, the HFDL group exhibited significantly greater BAT with concomitant reductions in WAT mass, serum lipid peroxides and serum glucose. No significant differences were observed in serum adipokines, inflammatory markers or UCP1 expression despite the aforementioned alterations in AT development. Results suggest that dietary lycopene supplementation may influence metabolic outcomes during the weaning and post-weaning periods. Additional research is warranted to elucidate molecular mechanisms by which lycopene influences AT biology.

Obesity is increasingly recognised as being a heterogeneous disease. Some obese individuals may present a metabolically healthy profile (metabolically healthy obese (MHO)), while some normal weight individuals exhibit an adverse cardiometabolic phenotype (metabolically unhealthy normal weight individuals (MUHNW)). The objectives of the present study were to examine the prevalence and associated characteristics of the different body composition phenotypes within a Maltese cohort. This was a cross-sectional analysis involving 521 individuals aged 41 ± 5 years. The metabolically unhealthy state was defined as the presence of ≥2 metabolic syndrome components (NCEP-ATPIII parameters), while individuals with ≤1 cardiometabolic abnormalities were classified as metabolically healthy. Overall, 70 % of the studied population was overweight or obese and 30⋅7 % had ≥2 cardiometabolic abnormalities. The prevalence of MHO and MUHNW was 10⋅7 and 2⋅1 %, respectively. Individuals with the healthy phenotype were more likely to consume alcohol, participate in regular physical activity and less likely to be smokers. While the MHO phenotype had similar values for waist, hip and neck circumferences, waist–hip ratio and insulin resistance when compared with MUHNW individuals, there was a lower proportion of MHO subjects having a high fasting plasma glucose, hypertriglyceridaemia or low HDL-C when compared with the unhealthy lean individuals. A high prevalence of the metabolically unhealthy phenotype was observed in this relatively young population which may result in significant future cardiovascular disease burden if timely assessment and management of modifiable risk factors are not implemented. Furthermore, the present study suggests that the MHO phenotype is not totally benign as previously thought.

Kefir consumption has been demonstrated to improve lipid and cholesterol metabolism; however, our previous study identified that benefits vary between different commercial and traditional kefir. Here, we investigate the ability of pitched culture kefir, that is, kefir produced by a small number of specific strains, to recapitulate health benefits of a traditional kefir, in a diet-induced obesity mouse model, and examine how microbial composition of kefir impacts these benefits. Eight-week-old female C57BL/6 mice were fed a high-fat diet (40 % energy from fat) supplemented with one of five kefir varieties (traditional, pitched, pitched with no Lactobacillus, pitched with no yeast and commercial control) at 2 ml in 20 g of food for 8 weeks prior to analysis of plasma and liver lipid profiles, and liver gene expression profiles related to lipid metabolism. Both traditional and pitched kefir lowered plasma cholesterol by about 35 % (P = 0·0005) and liver TAG by about 55 % (P = 0·0001) when compared with commercial kefir despite no difference in body weight. Furthermore, pitched kefir produced without either yeast or Lactobacillus did not lower cholesterol. The traditional and pitched kefir with the full complement of microbes were able to impart corresponding decreases in the expression of the cholesterol and lipid metabolism genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase, PPARγ and CD36 in the liver. These results demonstrate that traditional kefir organisms can successfully be utilised in a commercial process, while highlighting the importance of microbial interactions during fermentation in the ability of fermented foods to benefit host health.

Mycoprotein consumption has been shown to improve acute postprandial glycaemic control and decrease circulating cholesterol concentrations. We investigated the impact of incorporating mycoprotein into the diet on insulin sensitivity (IS), glycaemic control and plasma lipoprotein composition. Twenty healthy adults participated in a randomised, parallel-group trial in which they consumed a 7 d fully controlled diet where lunch and dinner contained either meat/fish (control group, CON) or mycoprotein (MYC) as the primary source of dietary protein. Oral glucose tolerance tests were performed pre- and post-intervention, and 24 h continuous blood glucose monitoring was applied throughout. Fasting plasma samples were obtained pre- and post-intervention and were analysed using quantitative, targeted NMR-based metabonomics. There were no changes within or between groups in blood glucose or serum insulin responses, nor in IS or 24 h glycaemic profiles. No differences between groups were found for 171 of the 224 metabonomic targets. Forty-five lipid concentrations of different lipoprotein fractions (VLDL, LDL, intermediate-density lipoprotein and HDL) remained unchanged in CON but showed a coordinated decrease (7–27 %; all P < 0·05) in MYC. Total plasma cholesterol, free cholesterol, LDL-cholesterol, HDL2-cholesterol, DHA and n-3 fatty acids decreased to a larger degree in MYC (14–19 %) compared with CON (3–11 %; P < 0·05). Substituting meat/fish for mycoprotein twice daily for 1 week did not modulate whole-body IS or glycaemic control but resulted in changes to plasma lipid composition, the latter primarily consisting of a coordinated reduction in circulating cholesterol-containing lipoproteins.

The aim of the study is to determine the differences in dietary parameters (energy and nutrient intake, adherence to the Mediterranean diet and consumption of food groups) in metabolically healthy overweight-obese (MHOO) v. metabolically unhealthy overweight-obese (MUOO) middle-aged adults. A total of fifty-one middle-aged adults were classified as MHOO or MUOO. BMI and blood pressure were evaluated following the recommendations. HDL, TAG and blood glycaemia were measured in blood samples. Blood pressure was also assessed. Dietary factors were assessed through three 24-h recalls, a validated FFQ and the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire. All variables were evaluated between September and October 2016 and 2017. Our results showed that MHOO individuals registered a higher fish consumption (P = 0·035) and higher compliance (lower consumption) in the commercial sweets and confectionery item of the PREDIMED questionnaire (P = 0·036). No differences were noted in other dietary factors including energy and nutrient intake, consumption of other food groups and in the PREDIMED total score. A near-significant trend toward significance was observed in nuts consumption, wine and fish items of the PREDIMED questionnaire. In conclusion, higher fish consumption and a higher compliance in the commercial sweets and confectionery item of the PREDIMED questionnaire were observed in MHOO middle-aged adults.

In this systematic review and meta-analysis of observational studies, we aimed to estimate the associations between prenatal vitamin D status and offspring growth, adiposity and metabolic health. We searched the literature in human studies on prenatal vitamin D status and offspring growth in PubMed, up to July 2017. Studies were selected according to their methodological quality and outcomes of interest (anthropometry, fat mass and diabetes in offspring). The inverse variance method was used to calculate the pooled mean difference (MD) with 95 % CI for continuous outcomes, and the Mantel–Haenszel method was used to calculate the pooled OR with 95 % CI for dichotomous outcomes. In all, thirty observational studies involving 35 032 mother–offspring pairs were included. Vitamin D status was evaluated by circulating 25-hydroxyvitamin D (25(OH)D) level. Low vitamin D status was based on each study’s cut-off for low 25(OH)D levels. Low prenatal vitamin D levels were associated with lower birth weight (g) (MD −100·69; 95 % CI −162·25, −39·13), increased risk of small-for-gestational-age (OR 1·55; 95 % CI 1·16, 2·07) and an elevated weight (g) in infant at the age of 9 months (g) (MD 119·75; 95 % CI 32·97, 206·52). No associations were observed between prenatal vitamin D status and other growth parameters at birth, age 1 year, 4–6 years or 9 years, nor with diabetes type 1. Prenatal vitamin D may play a role in infant adiposity and accelerated postnatal growth. The effects of prenatal vitamin D on long-term metabolic health outcomes in children warrant future studies.

Developmental origins of health and disease (DOHaD) is the study of how the early life environment can impact the risk of chronic diseases from childhood to adulthood and the mechanisms involved. Epigenetic modifications such as DNA methylation, histone modifications and non-coding RNAs are involved in mediating how early life environment impacts later health. This review is a summary of the Epigenetics and DOHaD workshop held at the 2016 DOHaD Society of Australia and New Zealand Conference. Our extensive knowledge of how the early life environment impacts later risk for chronic disease would not have been possible without animal models. In this review we highlight some animal model examples that demonstrate how an adverse early life exposure results in epigenetic and gene expression changes that may contribute to increased risk of chronic disease later in life. Type 2 diabetes and cardiovascular disease are chronic diseases with an increasing incidence due to the increased number of children and adults that are obese. Epigenetic changes such as DNA methylation have been shown to be associated with metabolic health measures and potentially predict future metabolic health status. Although more difficult to elucidate in humans, recent studies suggest that DNA methylation may be one of the epigenetic mechanisms that mediates the effects of early life exposures on later life risk of obesity and obesity related diseases. Finally, we discuss the role of the microbiome and how it is a new player in developmental programming and mediating early life exposures on later risk of chronic disease.

The prevalence of cardiometabolic diseases is a significant public health burden worldwide. Emerging evidence supports the inverse association between greater dairy consumption and reduced risk of cardiometabolic diseases. Dairy proteins may have an important role in the favourable impact of dairy on human health such as blood pressure (BP), blood lipid and glucose control. The purpose of this review is to update and critically evaluate the evidence on the impacts of casein and whey protein in relation to metabolic function. Evidence from short-term clinical studies assessing postprandial responses to milk protein ingestion suggests benefits on vascular function independent of BP, as well as improvement in glycaemic homeostasis. Long-term interventions have been less conclusive, with some showing benefits and others indicating a lack of improvement in vascular function. During chronic consumption BP appears to be lowered and both dyslipidaemia and hyperglacaemia seem to be controlled. Limited number of trials investigated the effects of dairy proteins on oxidative stress and inflammation. Although the underlying mechanisms of milk proteins on cardiometabolic homeostasis remains to be elucidated, the most likely mechanism is to improve insulin resistance. The incorporation of meals enriched with dairy protein in the habitual diet may result in the beneficial effects on cardiometabolic health. Nevertheless, future well-designed, controlled studies are needed to investigate the relative effects of both casein and whey protein on BP, vascular function, glucose homeostasis and inflammation.

Obesity-related metabolic conditions such as insulin resistance (IR), type 2 diabetes and CVD share a number of pathological features, one of which is metabolic-inflammation. Metabolic-inflammation results from the infiltration of immune cells into the adipose tissue, driving a pro-inflammatory environment, which can induce IR. Furthermore, resolution of inflammation, an active process wherein the immune system counteracts pro-inflammatory states, may be dysregulated in obesity. Anti-inflammatory nutritional interventions have focused on attenuating this pro-inflammatory environment. Furthermore, with inherent variability among individuals, establishing at-risk populations who respond favourably to nutritional intervention strategies is important. This review will focus on chronic low-grade metabolic-inflammation, resolution of inflammation and the putative role anti-inflammatory nutrients have as a potential therapy. Finally, in the context of personalised nutrition, the approaches used in defining individuals who respond favourably to nutritional interventions will be highlighted. With increasing prevalence of obesity in younger people, age-dependent biological processes, preventative strategies and therapeutic options are important to help protect against development of obesity-associated co-morbidities.

Evidence suggests that at a population level, childhood and adolescent obesity increase the long-term risk of chronic diseases such as type 2 diabetes and CVD. At an individual level, however, the metabolic consequences of obesity in youth vary immensely. Despite comparable BMI, some adolescents develop impaired glucose tolerance while others maintain normal glucose homeostasis. It has been proposed that the variation in the capacity to store lipid in the subcutaneous adipose tissue (SAT) may partially discriminate metabolically healthy from unhealthy obesity. In positive energy balance, a decreased capacity to expand SAT may drive lipid accumulation to visceral adipose tissue, liver and skeletal muscle. This state of lipotoxicity is associated with chronic low-grade inflammation, insulin resistance and dyslipidaemia. The present review examines the differential adipose tissue development and function in children and adolescents who exhibit metabolic dysregulation compared with those who are protected. Additionally, the role of manipulating dietary fat quality to potentially prevent and treat metabolic dysfunction in obesity will be discussed. The findings of the present review highlight the need for further randomised controlled trials to establish the effect of dietary n-3 PUFA on the metabolic phenotype of obese children and adolescents. Furthermore, using a personalised nutrition approach to target interventions to those at risk of, or those with established metabolic dysregulation may optimise the efficacy of modifying dietary fat quality.

Different dietary fat and energy subtypes have an impact on both the metabolic health and the intestinal microbiota population of the host. The present study assessed the impact of dietary fat quality, with a focus on dietary fatty acid compositions of varying saturation, on the metabolic health status and the intestinal microbiota composition of the host. C57BL/6J mice (n 9–10 mice per group) were fed high-fat (HF) diets containing either (1) palm oil, (2) olive oil, (3) safflower oil or (4) flaxseed/fish oil for 16 weeks and compared with mice fed low-fat (LF) diets supplemented with either high maize starch or high sucrose. Tissue fatty acid compositions were assessed by GLC, and the impact of the diet on host intestinal microbiota populations was investigated using high-throughput 16S rRNA sequencing. Compositional sequencing analysis revealed that dietary palm oil supplementation resulted in significantly lower populations of Bacteroidetes at the phylum level compared with dietary olive oil supplementation (P< 0·05). Dietary supplementation with olive oil was associated with an increase in the population of the family Bacteroidaceae compared with dietary supplementation of palm oil, flaxseed/fish oil and high sucrose (P< 0·05). Ingestion of the HF-flaxseed/fish oil diet for 16 weeks led to significantly increased tissue concentrations of EPA, docosapentaenoic acid and DHA compared with ingestion of all the other diets (P< 0·05); furthermore, the diet significantly increased the intestinal population of Bifidobacterium at the genus level compared with the LF-high-maize starch diet (P< 0·05). These data indicate that both the quantity and quality of fat have an impact on host physiology with further downstream alterations to the intestinal microbiota population, with a HF diet supplemented with flaxseed/fish oil positively shaping the host microbial ecosystem.

The number of people suffering from metabolic diseases is dramatically increasing worldwide. This stresses the need for new therapeutic strategies to combat this growing epidemic of metabolic diseases. A reduced mitochondrial function is one of the characteristics of metabolic diseases and therefore a target for intervention. Here we review the evidence that mitochondrial function may act as a target to treat and prevent type 2 diabetes mellitus, and, if so, whether these effects are due to reduction in skeletal muscle fat accumulation. We describe how exercise may affect these parameters and can be beneficial for type 2 diabetes. We next focus on alternative ways to improve mitochondrial function in a non-exercise manner. Thus, in 2003, resveratrol (3,5,4′-trihydroxystilbene) was discovered to be a small molecule activator of sirtuin 1, an important molecular target regulating cellular energy metabolism and mitochondrial homoeostasis. Rodent studies have clearly demonstrated the potential of resveratrol to improve various metabolic health parameters. Here we review data in human subjects that is available on the effects of resveratrol on metabolism and mitochondrial function and discuss how resveratrol may serve as a new therapeutic strategy to preserve metabolic health. We also discuss whether the effects of resveratrol are similar to the effects of exercise training and therefore if resveratrol can be considered as an exercise mimetic.