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Objective: Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide. Dietary interventions can directly affect several ASCVD risk factors. This study aimed to assess an association between dairy consumption and the odds of ASCVD and its risk factors in women with overweight and obesity., Methods: The present cross-sectional study was conducted on 390 Iranian women aged 18-48 years and body mass index (BMI) ≥ 25 kg/m². Dairy consumption was assessed using a 147-item food frequency questionnaire. Participants were divided into tertiles based on their dairy consumption with 130 (33.3%) women in each category., Results: The participants had an average age of 36.73 ± 9.18 years, and the mean BMI was 31.28 ± 4.30 kg/m 2 . In the unadjusted model, individuals in the third tertile of dairy consumption had 0.79 times lower odds of ASCVD compared to those in the first tertile (OR: 0.21; 95% Confidence Interval (CI): 0.11, 0.41; P-value = 0.001). Additionally, we observed a significant inverse relationship between higher dairy intake and adiposity markers, blood pressure, and Triglyceride glucose-body mass index (TyG-BMI)., Conclusion: The study revealed a negative association between dairy intake and the risk of ASCVD but this association diminished after adjusting for confounding factors. It also found a negative association between dairy consumption with BMI, fat mass index, body fat, blood pressure, and TyG-BMI., (© 2024. The Author(s).)

Aims: To examine association of liver-expressed antimicrobial peptide 2 (LEAP2), an endogenous ghrelin antagonist with anorexiant effects, to key cardiometabolic risk factors in people with overweight and obesity., Methods: In this cross-sectional study, we sought to identify associations between LEAP2 levels and cardiometabolic risk factors, including body composition (dual X-ray absorptiometry), insulin and glucose metabolism (oral and intravenous glucose tolerance tests and hyperinsulinaemic-euglycaemic clamps), plasma lipids and inflammation markers (ELISA and multiplex assays)., Results: In 65 participants with overweight or obesity (63.1% male, mean age 31.3 ± 8.5 years), LEAP2 levels were associated with total body fat, but not with body mass index or waist-hip ratio in both univariable and age- and sex-adjusted models (P < 0.05). Higher LEAP2 level was also positively associated with higher insulin secretion in univariable (P = 0.047) and multivariable models adjusted for age, sex and body fat (P = 0.03), but not with fasting glucose levels (P ≥ 0.05). Higher LEAP2 levels were associated insulin resistance (P = 0.07) after adjustment for age and sex, but the association disappeared after an additional adjustment for body fat (P = 0.2). There was an inverse association between LEAP2 levels and nuclear factor kappa-B (NFκB) activity in the peripheral blood mononuclear cells in age-, sex- and body fat-adjusted models (P = 0.04). There were no associations with cardiovascular risk factors (lipids, blood pressure) or other inflammation markers., Conclusions: These results provide important insights into the association between LEAP2 and cardiometabolic health in a high-risk population of individuals with overweight and obesity. This is a first report of an association between LEAP2 and insulin secretion, insulin sensitivity and NFκB activity. LEAP2 may represent an important potential therapeutic target to promote insulin secretion in people with type 2 diabetes and obesity., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose: Vitamin D supplementation may have non-skeletal health benefits and enhance exercise responsiveness, particularly in those with low vitamin D levels. We determined whether, compared with placebo, vitamin D supplementation taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight and obese older adults with vitamin D deficiency., Methods: Fifty overweight or obese older adults (mean ± SD age: 60 ± 6 years; BMI 30.6 ± 5.7 kg/m 2 ) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) were recruited. Participants were randomly allocated to receive either vitamin D 3 (4000 IU/day) or matching placebo for 24 weeks. Between weeks 12 and 24, all participants completed multi-modal exercise three days per week while continuing with vitamin D/placebo. Mean changes in physical function (primary outcome: gait speed), body composition and biochemical parameters at weeks 12 and 24 were compared between groups., Results: Vitamin D supplementation, with or without exercise, had no effect on gait speed. From baseline to week 12, vitamin D supplementation increased serum 25(OH)D levels (placebo: 2.5 ± 14.7 nmol/L; treatment: 43.4 ± 18.4 nmol/L; P < 0.001) and reduced stair climb times (placebo: 0.3 ± 1.0 s; treatment: - 0.2 ± 1.0 s; P = 0.046). From 12 to 24 weeks, vitamin D supplementation combined with exercise decreased waist circumference (placebo: 1.3 ± 7.3 cm; treatment: - 3.0 ± 6.1 cm; P = 0.02) and waist-to-hip ratio (placebo: 0.01 ± 0.05; treatment: - 0.03 ± 0.05; P = 0.01) relative to placebo. Vitamin D supplementation, with or without exercise, had no effect on other physical function, body composition or metabolic health outcomes., Conclusion: Vitamin D supplementation had no effect on most physical function, body composition or metabolic health parameters when taken alone, or during exercise, in overweight or obese older adults with vitamin D deficiency. Vitamin D-related improvements in stair climb times and waist circumference suggest that future trials should explore the effects of vitamin D on muscle power, and its effects on body composition when combined with exercise, in populations with moderate or severe vitamin D deficiency., (© 2022. The Author(s).)

Background/objectives: Obesity poses one of the biggest public health challenges globally. In addition to the high costs of obesity to the healthcare system, obesity also impacts work productivity. We aimed to estimate the benefits of preventing obesity in terms of years of life, productivity-adjusted life years (PALYs) and associated costs over 10 years., Subjects/methods: Dynamic life table models were constructed to estimate years of life and PALYs saved if all new cases of obesity were prevented among Australians aged 20-69 years from 2021 to 2030. Life tables were sex specific and the population was classified into normal weight, overweight and obese. The model simulation was first undertaken assuming currently observed age-specific incidences of obesity, and then repeated assuming all new cases of obesity were reduced by 2 and 5%. The differences in outcomes (years of life, PALYs, and costs) between the two modelled outputs reflected the potential benefits that could be achieved through obesity prevention. All outcomes were discounted by 5% per annum., Results: Over the next 10 years, 132 million years of life and 81 million PALYs would be lived by Australians aged 20-69 years, contributing AU$17.0 trillion to the Australian economy in terms of GDP. A 5% reduction in new cases of obesity led to a gain of 663 years of life and 1229 PALYs, equivalent to AU$262 million in GDP., Conclusions: Prevention of obesity is projected to result in substantial economic gains due to improved health and productivity. This further emphasises the need for public health prevention strategies to reduce this growing epidemic., (© 2022. The Author(s).)

Background: Weight-loss-induced fat loss improves cardiometabolic health in individuals with overweight and obesity; however, weight loss can also result in bone loss and increased fracture risk. Weight-loss-induced bone loss may be attenuated with exercise. Our aim was to compare changes in bone mineral density (BMD) in adults with overweight and obesity who undertook diet-induced weight loss alone or in combination with exercise., Methods: We included randomized controlled trials (RCTs) in adults with overweight or obesity (aged ≥18 years; body mass index ≥25 kg/m 2 ) that prescribed diet-induced weight loss alone or in combination with supervised exercise, and measured any bone structural parameters. Risk of bias was assessed using the Cochrane Risk of Bias tool. Random-effects meta-analyses determined mean changes and net mean differences (95% confidence intervals (95%CIs)) in the percentage of areal BMD (aBMD) change between groups., Results: We included 9 RCTs. Diet-induced weight loss led to significant losses in femoral neck aBMD (mean change: -1.73% (95%CI: -2.39% to -1.07%), p < 0.001) and total hip aBMD (-2.19% (95%CI: -3.84% to -0.54%), p = 0.009). Femoral neck aBMD losses were significantly greater in the diet-induced weight loss group compared to the exercise plus diet-induced weight loss group (net difference: -0.88% (95%CI: -1.73% to -0.03%)); however, there were no differences in aBMD changes at any other skeletal site: total hip (-1.96% (95%CI: -4.59% to 0.68%)) and lumbar spine (-0.48% (95%CI: -1.81% to 0.86%)). aBMD changes did not differ significantly according to exercise modality (resistance exercise, aerobic exercise, or a combination of the two) during diet-induced weight loss., Conclusion: Diet-induced weight loss led to greater femoral neck bone loss compared to diet-induced weight loss plus exercise. Bone loss at the total hip and lumbar spine was not attenuated by exercise during diet-induced weight loss. The lack of consistent skeletal benefits may be due to the insufficient duration and/or training intensities of most exercise interventions. Additional RCTs with appropriate, targeted exercise interventions should be conducted., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2021. Production and hosting by Elsevier B.V.)

Background: Back pain is the leading cause of disability worldwide and is associated with obesity and chronic low-grade inflammation. Alterations in intestinal microbiota may contribute to the pathogenesis of back pain through metabolites affecting immune and inflammatory responses. Aims and Methods: We compared the gut microbiota composition in a cohort of 36 overweight or obese individuals with or without self-reported back pain in the preceding month. Participants were characterized for anthropometry; bone health; metabolic health; inflammation; dietary intake; and physical activity. Results: Demographic, clinical, biochemical characteristics, diet and physical activity were similar between participants with ( n = 14) or without ( n = 22) back pain. Individuals with back pain had a higher abundance of the genera Adlercreutzia ( p = 0.0008; FDR = 0.027) , Roseburia ( p = 0.0098; FDR = 0.17), and Uncl. Christensenellaceae ( p = 0.02; FDR = 0.27) than those without back pain. Adlercreutzia abundance remained higher in individuals with back pain in the past 2 weeks, 6 months, and 1 year. Adlercreutzia was positively correlated with BMI (rho = 0.35, p = 0.03), serum adipsin (rho = 0.33, p = 0.047), and serum leptin (rho = 0.38, p = 0.02). Conclusions: Our findings suggest that back pain is associated with altered gut microbiota composition, possibly through increased inflammation. Further studies delineating the underlying mechanisms may identify strategies for lowering Adlercreutzia abundance to treat back pain., (Copyright © 2020 Dekker Nitert, Mousa, Barrett, Naderpoor and de Courten.)

Scope: Reduced amylase 1 (AMY1) copy numbers are associated with obesity, insulin resistance, and inflammation. Although mechanisms linking AMY1 copy number with metabolic disorders are poorly understood, recent findings suggest that lipids play a key role., Methods and Results: Plasma lipidomic signatures associated with AMY1 copy number are explored in 57 non-diabetic overweight/obese subjects aged 18-60. Serum amylase and inflammatory cytokines levels are also measured. AMY1 copy number is strongly associated with the serum amylase concentration. Participants are divided into low-(≤4) and high-(>4) AMY1 carriers based on the median. Low-AMY1 carriers have higher BMI and fat mass. They also have higher levels of dihexosylceramides (R = -0.27, p = 0.044), cholesterol esters (CE) (R = -0.32, p = 0.020), alkylphosphatidylcholines [PC(O)] (R = -0.33, p = 0.014), and sphingomyelins (SM) (R = -0.38, p = 0.005). From 459 lipid species, 28 differ between low- and high-AMY1 carriers. These include CE species with long-chain PUFA; PC(O) and PC plasmalogens containing arachidonic acid; and PC, mono-, di-, and tri-hexosylceramides, and SM containing saturated fatty acids (mainly C16:0 and C20:0). This lipidomic signature is strongly associated with inflammatory cytokines, which are also negatively associated with the AMY1 copy number., Conclusion: A lipidomics signature associated with low AMY1 copy numbers is revealed, which is linked to obesity and chronic low-grade inflammation., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Vitamin D regulates adipokine production in vitro; however, clinical trials have been inconclusive. We conducted secondary analyses of a randomized controlled trial to examine whether vitamin D supplementation improves adipokine concentrations in overweight/obese and vitamin D-deficient adults., Methods: Sixty-five individuals with a BMI ≥ 25 kg/m 2 and 25-hydroxyvitamin D (25(OH)D) ≤ 50 nmol/L were randomized to oral cholecalciferol (100,000 IU single bolus followed by 4,000 IU daily) or matching placebo for 16 weeks. We measured BMI, waist-to-hip ratio, % body fat (dual X-ray absorptiometry), serum 25(OH)D (chemiluminescent immunoassay) and total adiponectin, leptin, resistin, and adipsin concentrations (multiplex assay; flow cytometry). Sun exposure, physical activity, and diet were assessed using questionnaires., Results: Fifty-four participants completed the study (35M/19F; mean age = 31.9 ± 8.5 years; BMI = 30.9 ± 4.4 kg/m 2 ). After 16 weeks, vitamin D supplementation increased 25(OH)D concentrations compared with placebo (57.0 ± 21.3 versus 1.9 ± 15.1 nmol/L, p < 0.001). There were no differences between groups for changes in adiponectin, leptin, resistin, or adipsin in unadjusted analyses (all p > 0.05). After adjustment for baseline values, season, sun exposure, and dietary vitamin D intake, there was a greater increase in adiponectin (β[95%CI] = 13.7[2.0, 25.5], p = 0.02) and leptin (β[95%CI] = 22.3[3.8, 40.9], p = 0.02) in the vitamin D group compared with placebo. Results remained significant after additional adjustment for age, sex, and % body fat (p < 0.02)., Conclusions: Vitamin D may increase adiponectin and leptin concentrations in overweight/obese and vitamin D-deficient adults. Further studies are needed to clarify the molecular interactions between vitamin D and adipokines and the clinical implications of these interactions in the context of obesity., Clinical Trial Registration: clinicaltrials.gov: NCT02112721.

Purpose of Review: Lifestyle interventions (such as diet and physical activity) successfully limit excessive gestational weight gain and can reduce some adverse maternal events; however, benefit is variable and cost-effectiveness remains unclear. We aimed to review published cost-effectiveness analyses of lifestyle interventions compared with usual care on clinically relevant outcome measures. Five international and six grey-literature databases were searched from 2007 to 2018. Articles were assessed for quality of reporting. Data were extracted from healthcare and societal perspectives. Costs were adapted to the common currencies of Australia and the United Kingdom by adjusting for resource utilization, healthcare purchase price and changes in costs over time. Included studies were economic analyses of lifestyle interventions aiming to limit weight-gain during pregnancy and/or reduce risk of gestational diabetes, for women with a BMI of 25 or greater in pre- or early-pregnancy., Recent Findings: Of the 538 articles identified, six were retained for review: one modelling study and five studies in which an economic analysis was performed alongside a randomized-controlled trial. Outcome measures included infant birth-weight, fasting glucose, insulin resistance, gestational weight-gain, infant respiratory distress syndrome, perceived health, cost per case of adverse outcome avoided and quality-adjusted life years (QALYs). Interventions were cost-effective in only one study. Although many studies have investigated the efficacy of lifestyle interventions in pregnancy, few have included cost-effectiveness analyses. Where cost-effectiveness studies were undertaken, results were inconsistent. Secondary meta-analysis, taxonomy and framework research is now required to determine the effective components of lifestyle interventions and to guide future cost-effectiveness analyses.

Objectives: To determine sex-specific associations between insulin resistance and bone parameters measured by peripheral quantitative computed tomography in overweight and obese community-dwelling older adults., Study Design: Cross-sectional study of 79 community-dwelling overweight and obese adults (mean ± SD age 62.8 ± 7.9 years; body mass index 32.3 ± 6.1 kg/m 2 ; 58% women)., Main Outcome Measures: Peripheral quantitative computed tomography assessed distal radius and tibia trabecular volumetric bone mineral density (vBMD) and proximal radius and tibia cortical vBMD, periosteal circumference, endosteal circumference and stress-strain index. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated from fasting glucose and insulin values. Lean mass was assessed using dual-energy X-ray absorptiometry. Total minutes of moderate and vigorous physical activity (MVPA) were calculated using the Active Australia Survey., Results: Men and women in this cohort had no significant differences in fasting glucose and insulin concentrations, HOMA-IR values and diabetes prevalence (all P > 0.05). In women, HOMA-IR was positively correlated with proximal radius periosteal and endosteal circumference (r = 0.331; P = 0.034 and r = 0.325; P = 0.038, respectively). These associations became nonsignificant in multivariable regression analyses; however, HOMA-IR was negatively associated with proximal radius cortical vBMD (B = -4.79; 95% CI -8.66, -0.92) after adjusting for age, lean mass and MVPA. All associations between HOMA-IR and bone parameters became nonsignificant in a sensitivity analysis excluding individuals with diabetes, or self-reported use of glucose-lowering medications. There were no associations between HOMA-IR and bone parameters in men., Conclusions: Homeostatic Model Assessment of Insulin Resistance was negatively associated with radial cortical vBMD in overweight and obese older women, but not in men. Further studies are needed to clarify sex-specific associations between insulin resistance and bone health in overweight and obese older adults., (© 2019 John Wiley & Sons Ltd.)

This randomised placebo-controlled trial aimed to determine the effect of 16-weeks cholecalciferol supplementation on calcium-phosphate homeostasis and bone mineral density (BMD) in overweight and obese adults. Fifty-four vitamin D-deficient (25OHD<50 nmol/L), overweight and obese adults (mean age 32 ± 8.5 years) were included in the trial. Participants were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 weeks. Before and after the intervention, serum calcium, phosphate, 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH) and C-terminal plasma fibroblast growth factor-23 (cFGF-23) concentrations were measured. Whole-body BMD was assessed using dual-energy X-ray absorptiometry (DXA) and diet and sun exposure were assessed using self-administered questionnaires. There were no significant differences in baseline characteristics between the vitamin D and placebo group. After 16-weeks of vitamin D supplementation, mean changes in 25(OH)D concentration were higher in the vitamin D group (57 nmol/L 95% CI 49, 65) compared with placebo (2 nmol/L 95% CI -4, 8), P < 0.001. Additionally, iPTH concentrations declined in the vitamin D group (-1.19 pmol/L 95% CI -1.9, -0.47) compared with placebo (0.14 pmol/L 95% CI -0.49, 0.77), P = 0.006. There were no significant differences in calcium, phosphate, iPTH and cFGF-23 concentrations and whole-body BMD between vitamin D and placebo at follow-up. Inverse correlations were observed between mean change in serum iPTH and cFGF-23 in the vitamin D group only (r=-0.41, P = 0.029). In individuals with greater vitamin D deficiency at baseline (25(OH)D < 30 nmol/L), there was a significant increase in mean whole-body BMD (0.01 g/cm 2 , 95% CI 0.001, 0.025) however, the mean change in BMD was not different between vitamin D and placebo groups in this sub-group analysis. We conclude that cholecalciferol supplementation for 16 weeks increases serum 25(OH)D concentrations and reduces iPTH concentrations in overweight and obese, but otherwise healthy adults with vitamin D deficiency, and has no effect on calcium, phosphate and iFGF-23 concentrations and whole-body BMD., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Recent trials do not support a role for vitamin D supplementation in prevention or treatment of type 2 diabetes mellitus, although effects may differ in Asian populations. In this pilot secondary analysis of a placebo-controlled randomised trial of overweight or obese individuals with low 25-hydroxyvitamin D (25(OH)D < 50 nmol/L), we examined whether vitamin D supplementation improved insulin sensitivity or body composition in participants of Asian ethnicity. Amongst 65 trial participants, 33 reported being of Asian descent (mean ± SD age 30 ± 7 years; 67% male). Participants were block randomised to receive vitamin D (n = 14; initial bolus dose of 2500 μg cholecalciferol followed by 100 μg cholecalciferol/d) or placebo (n = 19; identical capsules) for 16 weeks. Primary outcome was change in insulin sensitivity (M-value) assessed by hyperinsulinemic-euglycemic clamp. Secondary outcomes were changes in 25(OH)D (chemiluminescent immunoassay), fasting blood glucose (YSI Stat 2300), and body composition including waist-hip ratio and total body fat percentage (dual-energy X-ray absorptiometry). Questionnaires assessed sun-exposure habits, physical activity, and diet. After the 16-week intervention, 25(OH)D concentrations increased significantly in the vitamin D group with no change in placebo (61.4 ± 21.1 vs -0.4 ± 12.7 nmol/L; P < 0.01). Vitamin D group participants demonstrated significant improvements in waist-hip ratio (-0.02 ± 0.03 vs 0.00 ± 0.02; P < 0.01) and fasting blood glucose (-0.1 ± 0.2 vs 0.2 ± 04 mmol/L; P < 0.04) compared with the placebo group, but changes in insulin sensitivity and other body composition measures did not differ significantly between groups (all P > 0.05). In conclusion, vitamin D supplementation improved waist-hip ratio and fasting blood glucose in overweight and obese Asian-Australians with low vitamin D concentrations. Further research is required to determine whether vitamin D supplementation is potentially more effective in specific ethnic groups., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Abnormalities of iron homeostasis have been linked to insulin resistance, type 2 diabetes and cardiovascular disease. Carnosine, an over-the-counter food supplement with chelating properties, has been shown to decrease serum iron and improve glucose metabolism in diabetic rodents. We have previously demonstrated that carnosine supplementation prevented worsening of glucose metabolism in healthy overweight and obese middle-aged adults. Yet, the impact of carnosine on markers of iron metabolism in humans has not been investigated. We aimed to determine whether carnosine supplementation has an effect on iron parameters in overweight and obese, otherwise healthy adults. We included 26 participants, who were randomly allocated to receive 1 g carnosine (n = 14) or identical placebo (n = 12) twice daily for 12 weeks. Iron parameters including iron, ferritin, transferrin, soluble transferrin receptor, total iron binding capacity and iron saturation were measured in serum or plasma by standard commercial assays. Carnosine supplementation decreased plasma soluble transferrin receptor compared to placebo (mean change difference ± standard error: - 0.07 ± 0.03 mg/l, p = 0.04). None of the other iron parameters were different between carnosine and placebo groups. At follow-up, soluble transferrin receptor was associated inversely with urinary carnosine concentrations and positively with serum carnosinase-1 activity (both p < 0.02). Our findings suggest that carnosine may modulate iron metabolism in high-risk groups which could ameliorate insulin resistance and prevent type 2 diabetes. Larger human clinical trials are required to confirm our results.

Obesity is partly driven by unhealthy food choices underpinned by cognitive biases, including approach bias (a tendency to move towards food cues) and delay discounting (a preference for immediate rewards). Cognitive training strategies aimed at modifying these biases, namely, approach-avoidance training (AAT) and episodic future thinking (EFT), may improve food choice. This pilot randomised trial examined the effect of these two trainings, delivered daily for 1 week via smartphone apps, on approach bias for healthy/unhealthy foods, delay discounting for money/food, and hypothetical food choice. Sixty overweight/obese participants (18-45 years) were randomly allocated to AAT, EFT, or control. Outcomes were measured at pretraining, posttraining, and 6-week follow-up. AAT reduced approach bias for unhealthy food and increased healthy food choice. However, EFT did not affect delay discounting or food choice. We conclude that AAT is useful for improving food choice in obesity and that smartphones are a feasible, engaging way to deliver training., (© 2018 John Wiley & Sons, Ltd and Eating Disorders Association.)

Vitamin D deficiency is prevalent in individuals with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis. However, there is limited and inconsistent data on the effect of vitamin D supplementation on liver function. Hepatic enzymes have been used as surrogate markers for NAFLD and have been associated with metabolic syndrome. We examined the relationships between 25-hydroxyvitamin D (25(OH)D) and γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP) in 120 drug-naïve individuals with no history of liver disease. In addition, the effect of vitamin D supplementation (100,000 loading dose of cholecalciferol followed by 4000IU daily for 16 weeks) on hepatic enzymes was investigated in a subgroup of 54 vitamin D-deficient overweight or obese individuals (28 randomised to cholecalciferol and 26 to placebo). Hepatic enzymes, anthropometric parameters, lipid profile, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp, M value) and high sensitivity C-reactive protein (hs-CRP) were measured before and after the intervention. In the cross-sectional study, levels of GGT and ALT were higher in men compared to women (both p=0.001). There were no significant differences in GGT, ALT and ALP between vitamin D categories (25(OH)D<25nmol/L, 25-50nmol/L, and >50nmol/L) and no relationships were found between the three enzymes and 25(OH)D before and after adjustment for age, sex, BMI, WHR, and insulin sensitivity (all p>0.5). In the randomised trial, 25(OH)D concentrations increased in the vitamin D group (mean change 57.0±21.3nmol/L) compared to the placebo group (mean change 1.9±15.1nmol/L). Mean changes in GGT, ALT and ALP were not significantly different between vitamin D and placebo groups (all p>0.2). Change in 25(OH)D concentration was not correlated with changes in GGT, ALT and ALP before and after adjustments for age and sex (all p>0.1). In summary, 25(OH)D concentrations were not related to hepatic enzymes in drug-naive adults with no history of liver disease, and vitamin D supplementation had no effect on the serum levels of hepatic enzymes in vitamin D-deficient and overweight or obese, otherwise healthy individuals. Hence, vitamin D supplementation is unlikely to prevent incident NAFLD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Recent evidence suggests that vitamin D deficiency may contribute to increased risk of depression. However, previous studies are limited by variability in participant characteristics including vitamin D deficiency status and presence of existing diseases, use of low doses of vitamin D supplementation for short durations, and use of co-interventions or psychotropic drugs. We examined whether 25-hydroxyvitamin D (25(OH)D) concentrations were associated with symptoms of depression, as well as whether vitamin D supplementation reduced symptoms of depression in overweight or obese and vitamin D-deficient, but otherwise healthy adults. Cross-sectional analyses were performed on baseline data from 63 (39M/24F) overweight or obese (body mass index (BMI) ≥25kg/m 2 ) and vitamin D-deficient (25(OH)D ≤50 nmol/l) adults (mean age=31.3±8.5), without clinical depression. Participants were randomized to either a bolus oral dose of 100,000 IU followed by 4000 IU daily of cholecalciferol, or matching placebo for 16 weeks. Interventional analyses were performed on data from 48 participants (30M/18F) who completed the trial. We measured serum 25(OH)D concentrations; anthropometry: BMI, waist-to-hip ratio (WHR), % body fat (dual X-ray absorptiometry); and depressive symptoms using the Beck Depression Inventory (BDI) before and after intervention. Data on dietary vitamin D intake (3-day food record), physical activity (international physical activity questionnaire), and sun exposure habits were collected using questionnaires. At baseline, mean 25(OH)D concentration was 32.9±11.3 nmol/l and total BDI score was 6.6±6.3 (range=0-33). There were no associations between 25(OH)D concentrations and total BDI scores or BDI subscales (all p>0.1). After the 16-week intervention, 25(OH)D concentrations increased in the vitamin D group compared to placebo (56.0±20.8 versus 2.7±13.9 nmol/L, respectively; p <0.0001). Change in total BDI scores did not differ between vitamin D and placebo groups (-2.0±4.5 versus -1.5±2.9, respectively; p=0.7). There were no differences in BDI subscales between groups (both p>0.1). Results remained non-significant after adjusting for multiple covariates including sun exposure, physical activity, and dietary vitamin D intake (all p>0.1). Our findings suggest that vitamin D deficiency may not be related to increased risk of depression in individuals without clinically significant depression and that the use of vitamin D supplementation may not be warranted for reducing depressive symptoms in this population. Further large-scale studies are needed to establish whether vitamin D supplementation may be beneficial for improving depressive symptoms in other population groups, including in those with existing depressive or psychiatric disorders., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Carnosine has been shown to reduce oxidation and glycation of low density lipoprotein hence improving dyslipidaemia in rodents. The effect of carnosine on human plasma lipidome has thus far not been investigated. We aimed to determine whether carnosine supplementation improves the plasma lipidome in overweight and obese individuals. Lipid analysis was performed by liquid chromatography mass spectrometry in 24 overweight and obese adults: 13 were randomly assigned to 2 g carnosine daily and 11 to placebo, and treated for 12 weeks. Carnosine supplementation maintained trihexosylceramide (0.01 ± 0.19 vs -0.28 ± 0.34 nmol/ml, p = 0.04), phosphatidylcholine (77 ± 167 vs -81 ± 196 nmol/ml, p = 0.01) and free cholesterol (20 ± 80 vs -69 ± 80 nmol/ml, p = 0.006) levels compared to placebo. Trihexosylceramide was inversely related with fasting insulin (r = -0.6, p = 0.002), insulin resistance (r = -0.6, p = 0.003), insulin secretion (r = -0.4, p = 0.05) and serum carnosinase 1 activity (r = -0.3, p = 0.05). Both phosphatidylcholine and free cholesterol did not correlate with any cardiometabolic parameters. Our data suggest that carnosine may have beneficial effects on the plasma lipidome. Future larger clinical trials are needed to confirm this.

Scope: Maternal vitamin D deficiency has been implicated in adverse pregnancy outcomes. However, the association between vitamin D and inflammation, particularly adipokines, remains unexplored in pregnancy., Methods and Results: In 102 overweight or obese pregnant women at high-risk of gestational diabetes mellitus (GDM), we investigated relationships between maternal 25-hydroxyvitamin D (25(OH)D) concentrations at 12-15 wk gestation (baseline) and serum lipids, inflammatory markers, novel adipokines (omentin-1, visfatin, high molecular weight (HMW) adiponectin), and subsequent pregnancy outcomes (GDM, preeclampsia, preterm birth [PTB]). After adjustment for maternal factors (age, BMI, parity, ethnicity, and smoking status), baseline 25(OH)D concentrations were inversely associated with total cholesterol and triglycerides, and positively associated with HMW-adiponectin. Higher baseline 25(OH)D concentrations were associated with decreased fasting and 1-h post-OGTT glucose and reduced risk of GDM at 26-28 wk, as well as with longer gestation and reduced risk of PTB upon additional adjustment for caesarean section. Adding HMW-adiponectin to the multivariable models attenuated most associations, and HMW-adiponectin was a significant predictor in the models., Conclusion: Our findings suggest that lower maternal 25(OH)D concentrations in overweight/obese pregnant women at high-risk of GDM are associated with increased cardiometabolic risks during pregnancy and adverse pregnancy outcomes, and that these associations may be mediated by HMW-adiponectin., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vitamin D deficiency has reached epidemic proportions worldwide and has recently been linked to cardiometabolic risk factors including obesity, insulin resistance, hypertension, dyslipidemia, as well as type 2 diabetes and cardiovascular disease. The objective of this study was to examine the associations between circulating 25-hydrovitamin D (25(OH)D) levels and cardiometabolic risk factors using direct measures of adiposity, glucose intolerance, and insulin resistance, as well as lipids, blood pressure, and plasma markers of inflammation. We measured circulating 25(OH)D, physical activity (International Physical Activity Questionnaire- IPAQ), anthropometry (body mass index (BMI), waist-to-hip ratio (WHR), % body fat (dual energy X-ray absorptiometry)), metabolic parameters (fasting and 2-h plasma glucose levels during oral glucose tolerance test; insulin sensitivity (M, hyperinsulinaemic-euglycaemic clamp), and cardiovascular and inflammatory profiles (blood pressure (BP), pulse pressure (PP), mean arterial pressure (MAP), plasma lipid levels, white blood cell count (WBC), and plasma high-sensitivity C-reactive protein levels (hsCRP)) in 111 healthy, non-diabetic adults (66 males/45 females; age 31.1±9.2years; % body fat 36.0±10.2%). Mean 25(OH)D was 39.8±19.8 nmol/L with no difference between genders (p=0.4). On univariate analysis, 25(OH)D was associated with% body fat (r=-0.27; p=0.005), 2-h glucose (r=-0.21; p=0.03), PP (r=0.26; p=0.006), and insulin sensitivity (r=0.20, p=0.04), but not with age, BMI, WHR, fasting glucose, BP, MAP, lipids, or inflammatory markers (all p>0.05). After adjusting for age and sex, 25(OH)D remained associated with% body fat (β=-0.12%; p=0.003), 2-h glucose (β=-0.13mmol/L; p=0.02), PP (β=0.12mmHg; p=0.009), and insulin sensitivity (β=0.22mg/kg/min; p=0.03), and became associated with fasting glucose (β=-0.04mmol/L; p=0.04) and hsCRP (β=-0.51mg/L; p=0.04). After adjusting for age, sex, and % body fat, 25(OH)D was no longer associated with insulin sensitivity, 2-h glucose, or hsCRP, but remained associated with fasting glucose (β=-0.05mmol/L; p=0.03) and PP (β=0.10mmHg; p=0.03). 25(OH)D remained associated with fasting glucose (β=-0.06mmol/L; p=0.02) after hsCRP and physical activity were added to the model with % body fat, age, and sex. ​These cross-sectional data suggest that associations between vitamin D and cardiometabolic risk among healthy, non-diabetic adults are largely mediated by adiposity. Large-scale intervention and mechanistic studies are needed to further investigate whether vitamin D has an independent role in the prevention and/or management of cardiometabolic risk and disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To determine factors associated with differential changes in body fat, insulin resistance and aerobic capacity following a 12-week exercise intervention in overweight and obese women with and without polycystic ovary syndrome (PCOS)., Methods: 16 overweight and obese women (9 PCOS; 7 without PCOS) completed a supervised progressive 12-week exercise program. Primary outcomes included changes in indicators of insulin sensitivity (including glucose infusion rate relative to fat-free mass [GIR/FFM]), body composition, and aerobic capacity (VO2 peak; 12 participants only). Comparisons were made between women with and without PCOS, and between participants who lost ≥5% (classified as exercise responders) and <5% (non-responders) in body fat (assessed by dual-energy X-ray absorptiometry)., Results: Training decreased body fat percentage by (mean; 95% CI) -2.3%; -5.3, 0.7% in women with PCOS and by -6.4%; -10.9, -1.9% in women without PCOS (P = 0.08). Ten women (7 PCOS; 3 without PCOS) did not reduce body fat by ≥5%. All participants improved VO2 peak (mean change 27%; 16-39%) but four (2 PCOS; 2 without PCOS) demonstrated decreases in GIR/FFM (mean change for whole cohort: 37%; 3-71%). Android-gynoid fat ratio (0.58; 0.51, 0.66 vs 0.46; 0.40, 0.51; P<0.01) was significantly higher and GIR/FFM (6.69; 3.49, 9.90 vs 11.44; 9.15, 13.72 mg/kg/min; P = 0.01) was significantly lower in non-responders compared with responders at baseline, but non-responders had significant post-training decreases in android-gynoid ratio (-0.02; -0.04, -0.01; P = 0.03), and increases in VO2 peak (7.24; 2.28, 12.21 mL/kg/min; P = 0.01) and GIR/FFM (1.44; 0.27, 2.61 mg/kg/min; P = 0.02). In women with PCOS, pre-training VO2 peak was significantly negatively correlated with change in total body fat (r = -0.75; P = 0.02), and pre-training fasting glucose negatively correlated with changes in VO2 peak (r = -0.76; P = 0.04), but positively correlated with changes in GIR (r = 0.67; P = 0.046)., Conclusion: A high proportion of overweight and obese women with PCOS had small reductions in body fat following a 12-week exercise intervention, but nevertheless significantly reduced relative central adiposity and improved aerobic capacity and insulin sensitivity.

Diets high in advanced glycation end products (AGEs) are thought to be detrimental to cardiovascular health. However, there remains uncertainty about the beneficial effect of a low AGE diet on cardiovascular risk factors and inflammatory markers in overweight individuals. We thus performed a randomised, double blind, crossover trial to determine whether consumption of low AGE diets reduce inflammation and cardiovascular risks in overweight and obese otherwise healthy adults. All participants (n = 20) consumed low and high AGE diets alternately for two weeks and separated by a four week washout period. Low AGE diets did not change systolic (p = 0.2) and diastolic blood pressure (p = 0.3), mean arterial pressure (p = 0.8) and pulse pressure (p = 0.2) compared to high AGE diets. Change in total cholesterol (p = 0.3), low-density lipoprotein (p = 0.7), high-density lipoprotein (p = 0.2), and triglycerides (p = 0.4) also did not differ and there was no difference in inflammatory markers: interleukin-6 (p = 0.6), monocyte chemoattractant protein-1 (p = 0.9), tumour necrosis factor α (p = 0.2), C-reactive protein (p = 0.6) and nuclear factor kappa beta (p = 0.2). These findings indicate that consumption of low AGE diets for two weeks did not improve the inflammatory and cardiovascular profiles of overweight and obese adults.

Glomerular hyperfiltration has been associated with obesity, insulin resistance, and systolic blood pressure (SBP). However, previous studies are limited by confounders such as pre-existing diabetes or hypertension, or have used indirect measures of adiposity and insulin sensitivity (IS). Therefore, we examined the relationship between estimated glomerular filtration rate (eGFR) and IS measured by the hyperinsulinaemic euglycaemic clamp in a healthy population on no medications. We performed oral glucose tolerance test (OGTT) and measured % body fat (DEXA), BMI, blood pressure and M-value (hyperinsulinaemic euglycaemic clamp) in 104 individuals (44 females and 60 males). The majority of the study population (n = 89, 85.6%) were classified on their BMI as overweight/obese. eGFR was related to age, BMI, M-value (IS), 2-hour glucose levels post OGTT and white blood cell count (WBC) (all p < 0.05); but not to SBP (p = 0.1) or fasting glucose levels (p = 0.2). After adjustment for gender, BMI, SBP and WBC, the inverse association between eGFR and M-value (p = 0.001), and 2-hour glucose post OGTT (p = 0.02) persisted. In conclusion, although eGFR has been associated with BMI and blood pressure in previous studies, in our healthy population, eGFR was more closely related to markers of glucose metabolism (IS and 2-hour glucose post OGTT) than to BMI and blood pressure.

Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species.

Background: The consumption of advanced glycation end products (AGEs) has increased because of modern food processing and has been linked to the development of type 2 diabetes in rodents., Objective: We determined whether changing dietary AGE intake could modulate insulin sensitivity and secretion in healthy, overweight individuals., Design: We performed a double-blind, randomized, crossover trial of diets in 20 participants [6 women and 14 men; mean ± SD body mass index (in kg/m(2)): 29.8 ± 3.7]. Isoenergetic- and macronutrient-matched diets that were high or low in AGE content were alternately consumed for 2 wk and separated by a 4-wk washout period. At the beginning and end of each dietary period, a hyperinsulinemic-euglycemic clamp and an intravenous glucose tolerance test were performed. Dietary, plasma and urinary AGEs N(€)-(carboxymethyl)lysine (CML), N(€)-(carboxyethyl)lysin (CEL), and methylglyoxal-derived hydroimadazolidine (MG-H1) were measured with the use of mass spectrometry., Results: Participants consumed less CML, CEL, and MG-H1 during the low-AGE dietary period than during the high-AGE period (all P < 0.05), which was confirmed by changes in urinary AGE excretion. There was an overall difference in insulin sensitivity of -2.1 mg · kg(-1) · min(-1) between diets (P = 0.001). Insulin sensitivity increased by 1.3 mg · kg(-1) · min(-1) after the low-AGE diet (P = 0.004), whereas it showed a tendency to decrease by 0.8 mg · kg(-1) · min(-1) after the high-AGE diet (P = 0.086). There was no difference in body weight or insulin secretion between diets (P = NS)., Conclusions: A diet that is low in AGEs may reduce the risk of type 2 diabetes by increasing insulin sensitivity. Hence, a restriction in dietary AGE content may be an effective strategy to decrease diabetes and cardiovascular disease risks in overweight individuals. This trial was registered at clinicaltrials.gov as NCT00422253., (© 2016 American Society for Nutrition.)

Background: Despite Australia's sunny climate, low vitamin D levels are increasingly prevalent. Sun exposure is limited by long working hours, an increase in time spent indoors, and sun protection practices, and there is limited dietary vitamin D fortification. While the importance of vitamin D for bone mineralization is well known, its role as a protective agent against chronic diseases, such as type 2 diabetes and cardiovascular disease, is less understood. Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion, mainly via its anti-inflammatory properties, thereby decreasing the risk of development and progression of type 2 diabetes. The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D (25(OH)D), obtained through vitamin D supplementation, will increase insulin sensitivity and insulin secretion. A secondary aim is to determine whether these relationships are mediated by a reduction in underlying subclinical inflammation associated with obesity., Methods/design: Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old, with low vitamin D levels (25(OH)D < 50 nmol/l), will be randomly assigned to intervention or placebo. At baseline, participants will undergo a medical review and anthropometric measurements, including dual X-ray absorptiometry, an intravenous glucose tolerance test, muscle and fat biopsies, a hyperinsulinemic euglycemic clamp, and questionnaires assessing diet, physical activity, sun exposure, back and knee pain, and depression. The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D (cholecalciferol) daily, while the placebo group will receive apparently identical capsules, both for a period of 16 weeks. All measurements will be repeated at follow-up, with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group. Secondary outcome measures will compare changes in anthropometry, cardiovascular risk factors, and inflammatory markers., Discussion: The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms, which are relevant for the prevention and management of type 2 diabetes., Trial Registration: Clinicaltrials.gov ID: NCT02112721 .

OBJECTIVE High-heat cooking of food induces the formation of advanced glycation end products (AGEs), which are thought to impair glucose metabolism in type 2 diabetic patients. High intake of fructose might additionally affect endogenous formation of AGEs. This parallel intervention study investigated whether the addition of fructose or cooking methods influencing the AGE content of food affect insulin sensitivity in overweight individuals. RESEARCH DESIGN AND METHODS Seventy-four overweight women were randomized to follow either a high- or low-AGE diet for 4 weeks, together with consumption of either fructose or glucose drinks. Glucose and insulin concentrations-after fasting and 2 h after an oral glucose tolerance test-were measured before and after the intervention. Homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index were calculated. Dietary and urinary AGE concentrations were measured (liquid chromatography tandem mass spectrometry) to estimate AGE intake and excretion. RESULTS When adjusted for changes in anthropometric measures during the intervention, the low-AGE diet decreased urinary AGEs, fasting insulin concentrations, and HOMA-IR, compared with the high-AGE diet. Addition of fructose did not affect any outcomes. CONCLUSIONS Diets with high AGE content may increase the development of insulin resistance. AGEs can be reduced by modulation of cooking methods but is unaffected by moderate fructose intake.