Metabolic Health Disorders Research Articles

Evaluation of metabolic changes in clinic attendees with therapeutic carbohydrate restriction

Background: Obesity and related metabolic health disorders are major clinical problems that have become increasingly prevalent worldwide.Aim: This before-after study examined the impact of therapeutic carbohydrate restriction (TCR) in managing metabolic health and promoting weight loss in a clinical setting using indirect calorimetry (IC).Setting: Data were collected from medical records obtained from a specialised allied health clinic focusing on metabolic health.Methods: The study analysed retrospective data from 202 overweight or obese participants (77% female, mean age 47.3) who received TCR as part of a behavioural modification programme involving multiple visits where their lifestyle, body composition and respiratory quotient (RQ), a key indicator of fat oxidation were recorded.Results: The study found that TCR improved fat oxidation in 84% of participants at short term visit (around 2 weeks), with an average weight loss of 1.8 kg. At medium term visit (around 12 weeks), 82% of participants maintained an increase in fat oxidation rate, with an average weight loss of 3.9 kg. In addition, among those with recorded body composition and waist circumference, 71% of weight lost was from fat, with an average reduction of 4.9 cm in waist measurements.Conclusion: This real-world study suggests that personalised TCR guided by IC can be an effective strategy for improving metabolic flexibility to help manage excess weight and related co-morbidities in a free-living population. Further research is needed to examine the long-term effects of TCR using this approach.Contribution: The utilisation of IC allows for the examination of individual shifts and improvements in metabolism among patients undergoing TCR.

Stepwise evaluation for the risk of metabolic unhealthiness and significant non-alcoholic fatty liver disease in India

Non-communicable diseases including metabolic health disorders are becoming area of concern for low/middle income countries with poor health-care resources. Present study was planned to assess the prevalence of metabolically unhealthy (MU) subjects in the community and proportion of the MU subjects having the risk of significant Non-alcoholic Fatty Liver Disease (NAFLD) using a step-wise evaluation strategy in a resource-poor setting. Study was performed in 19 community development blocks of Birbhum district, West Bengal, India. Every fifth member in the electoral list was included for the first step evaluation (n = 79,957/1,019,365, 7.8%) to detect any metabolic risk. Subjects with any metabolic risk in the first step (n = 9819/41,095, 24%) were taken for second step evaluation with Fasting blood glucose (FBG) and ALT. Subjects with elevated FBG and/or ALT in the second step (n = 1403/5283, 27%) were taken into third step evaluation. At least one risk factor was found in 51.4% (n = 41,095/79,957). 63% (n = 885/1403) of the subjects with metabolic abnormality (third step) had MU state making its overall prevalence of 1.1% (n = 885/79,957). 53% of MU subjects (n = 470/885) had ‘persistently elevated ALT’ suggesting the risk of having significant NAFLD. Step-wise evaluation strategy could detect the subjects at risk, actually having MU state and proportion of MU subjects at risk of having ‘persistently elevated ALT’ (surrogate of significant NAFLD) in the community with minimum utilization of scarce resources. This study was funded by Bristol Myers Squibb Foundation, USA, under the program ‘Together on Diabetes Asia’ (Project Number: 1205 – LFWB).

Breaking the vicious cycle: The interplay between loneliness, metabolic illness, and mental health.

Loneliness, or perceived social isolation, is a leading predictor of all-cause mortality and is increasingly considered a public health epidemic afflicting significant portions of the general population. Chronic loneliness is itself associated with two of the most pressing public health epidemics currently facing the globe: the rise of mental illness and metabolic health disorders. Here, we highlight the epidemiological associations between loneliness and mental and metabolic health disorders and argue that loneliness contributes to the etiology of these conditions by acting as a chronic stressor that leads to neuroendocrine dysregulation and downstream immunometabolic consequences that manifest in disease. Specifically, we describe how loneliness can lead to overactivation of the hypothalamic-pituitary-adrenal axis and ultimately cause mitochondrial dysfunction, which is implicated in mental and metabolic disease. These conditions can, in turn, lead to further social isolation and propel a vicious cycle of chronic illness. Finally, we outline interventions and policy recommendations that can reduce loneliness at both the individual and community levels. Given its role in the etiology of the most prevalent chronic diseases of our time, focusing resources on alleviating loneliness is a vitally important and cost-effective public health strategy.

Exploring the Profile of the Gut Microbiome in Differentiating Type 2 Diabetes Mellitus and Non Alcoholic Fatty Liver Disease

Type 2 Diabetes Mellitus (T2DM) and Non Alcoholic Fatty Liver Disease (NAFLD) are emerging global pandemics and carry a significant burden of co-morbidity and mortality. Asian Indians have the highest prevalence of T2DM, leading to 2.54 million deaths yearly. In India, it is 11.6%, and 30-50% of patients with NAFLD have diabetes. Patients with worsening T2DM tend to have increased progression of NAFLD to cirrhosis. NAFLD leads to end-stage liver disease causing 2.59 million deaths annually. Therefore, the relationship between T2DM and NAFLD needs to be disclosed, and the gut microbiome shows significant characteristics for the same. The gut microbiome is a collection of trillions of bacteria, archaea and fungi that resides in the digestive tract of humans. It plays a significant role in health by helping control digestion and benefits our immune system. Progression of metabolic health disorders shows changes in the quality and heterogeneity of the gut microbiome. It has been established that metabolic and immunological disorders are mainly influenced by the gut microbiome and not by the type of diet. Butyrate-producing bacteria benefit insulin resistance leading to more chances of T2DM. Since, the liver is close to the gut microbiome, the influence of the gut microbiome and its metabolites affecting liver function is great. But, gut microbiome being specific in both cases can assist in exploring the relationship and differentiating one from the other. Therefore, further analysis and studies are required to understand the role of the gut microbiome and its significance in better diagnosis.

Early-Life Sugar Consumption Affects the Microbiome in Juvenile Mice.

The composition of the gut microbiota is influenced by the dietary nutrient. Sugar has been linked with many metabolic health disorders such as heart disease, metabolic syndrome, and immune disorders. Long-term consumption of sugar influences the landscape of gut microbiota by altering the gut microbial population called dysbiosis. This study aims to evaluate the impact of long-term consumption of high sugar diet (HSD) on the diversity of gut microbiota. CD1 mice are given high concentration of sugar for 15weeks followed by a recovery period of 10weeks. Real-time polymerase chain reaction and 16S rRNA next-generation sequencing methods employ to identify microbiome diversity. The results show that Firmicutes and Bacteroidetes are the predominant phyla in control, cecum, and fecal samples. Firmicutes population are gradually increased in treated samples even after the recovery period, whereas Bacteroidetes abundance slightly reduces throughout the study. The present study shows that the impact of long period of high sugar diet consumption alters the diversity of normal gut flora which can be restored after 10weeks of sugar withdrawal. This indicates that the intervention of healthy and nutritious diet influences gut microbes and this can be beneficial in reducing the implication of early life metabolic disorders such as obesity.

Autophagy modulation in resveratrol protective effects on steroidogenesis in high-fat diet-fed mice and H2O2-challenged TM3 cells.

Autophagy dysregulation and oxidative stress play critical pathophysiological roles in developing obesity-related metabolic health disorders. This study aims to investigate how autophagy modulationis related to resveratrol (RSV) antioxidant activities and preventive effects on steroidogenesis decline associated with a high-fat diet (HFD) and oxidative damage. Eight-week-old C57BL/6J male mice were fed with HFD with or without supplement RSV (400mg/kg/day) by gavage for 16weeks. The control group was fed with a standard diet with no RSV or the same amount of RSV. Mouse Leydig cell line TM3 cell was used for in vitro studies. Oxidative stress was induced in TM3 cells with H2O2, followed by RSV treatment plus autophagy activator rapamycin or autophagy inhibitor 3-methyladenine, respectively. RSV supplement could upregulate proteins level of StAR and mitochondrial proteins COX4 and mtTFA, indicating the amelioration of steroidogenesis decline and mitochondrial dysfunction caused by HFD. Antioxidants such as GPx4 and SOD2 were improved by RSV as well. The observation of autophagosomes and the changes in expressions of LC3II/I, Beclin1, and Atg7 indicated that RSV could reverse the autophagy defect associated with HFD. 3-methyladenine inhibition of autophagy partially abolished RSV protection on mitochondrial function and steroidogenesis in H2O2-challenged TM3 cells. However, the combination use of rapamycin and RSV did not improve protection on Leydig cells against oxidative damage. The stimulation of autophagy by RSV is closely linked to its antioxidant actions and positive impact on steroidogenesis in HFD mice. The findings suggest RSV is protective against obesity-related Leydig cell impairment.

РАЗВИТИЕ ОТДАЛЕННЫХ ПОСЛЕДСТВИЙ В ВИДЕ ПАТОЛОГИЙ ЖЕЛУДОЧНО-КИШЕЧНОГО ТРАКТА У ПАЦИЕНТОВ, ПРОХОДИВШИХ СПЕЦИАЛЬНОЕ ЛЕЧЕНИЕ ПО ПОВОДУ ДИФФЕРЕНЦИРОВАННОГО РАКА ЩИТОВИДНОЙ ЖЕЛЕЗЫ

Objective. Evaluate the potential long-term effects of differentiated thyroid cancer (DTC) treatment, on the gastro-intestinal tract (GIT) based on a retrospective study of DTC patients. Methods. Occurrence of long-term GIT pathologies was retrospectively studied in 157 DTC patients. All patients were treated according to the standard of care, which includes radical surgery, radiation therapy and hormone therapy. The database contained digitalised medical histories of patients followed for at least 1 year after treatment. A total of 463 entries were available, representing one entry per noted consequence for each of the 157 patients. The study focused on two aspects. The frequencies of complications before and after treatment were compared, and factors impacting DTC pathology in a statistically significant manner were isolated. Results: The total onset frequency of gallbladder, liver and pancreas disorders was increased by a factor of 1.6 in a statistically significant manner in DTC patients. Patients initially presenting gallbladder disorders received shorter cures of hormone therapy (4 versus 13 months), and lower levels of L-thyroxine in a context of uncompensated hypothyroidism (2.3 versus 3.5 mg/kg). A statistically significant relation was established between the total duration of breastfeeding in women presenting metabolic health disorders, and onset of liver pathology (essentially non-alcoholic steatohepatitis). Conclusion. Life-long GIT pathology monitoring should be standard of care for patients after special DTC treatment. What this paper adds The long-term effects of treatment of differentiated thyroid cancer on the gastro-intestinal tract have never been described to date. Here, a 1.6-fold increase in disorders implicating mainly the gallbladder, liver and pancreas is noted. Gallbladder disorders are shown to be frequent in patients undergoing short courses of thyroid hormone suppression therapy with low levels of L-thyroxine and presenting uncompensated hypothyroidism. In women presenting metabolic disorders, a relation has been established between the total duration of breastfeeding and the later development of liver pathologies.

Role of Tinospora cordifolia in metabolic health disorders: An updated review

The use of various herbal drugs in India has been widely developed in recent years. Guduchi (Tinospora cordifolia) belonging to family Menispermaceae has a tremendous amount of bioactive principles in exploring nutraceuticals from natural source. T. cordifolia is considered as an important herbal drug of traditional system of Indian Medicines. The herb is also well known for its therapeutic efficacy in treatment of various diseases viz. dyspepsia, diabetes, fever, urinary problems, jaundice, chronic diarrhoea, cardiac disease, dysentry, helmenthiasis, skin diseases, leprosy, thyroidand various metabolic diseases. Present review highlights the antidiabetic, hypolipidemic activity of Guduchi and their validation through existing literature, experimental studies. The plant is reported to have various alkaloids, glycosides, steroids and terpenoids. The current study is undertaken to explore and review its role on metabolic disorders.

Sex differences in the developmental origins of cardiometabolic disease following exposure to maternal obesity and gestational diabetes 1.

Over the past 30 years, the worldwide prevalence of obesity has nearly doubled. In addition, more and more women in their child-bearing years are overweight or obese, which increases the risk of gestational diabetes mellitus (GDM). It is increasingly accepted by the scientific community that early life exposure to environmental stress influences the long-term health of an individual, which has been termed the Developmental Origins of Health and Disease theory. Evidence from human cohorts and epidemiological and animal studies has shown that maternal obesity and GDM condition the offspring for cardiometabolic disease development. These effects are most likely regulated by epigenetic mechanisms; however, biological sex is an important factor in defining the risk of the development of several metabolic health disorders. The aim of this review is to describe the current evidence from human cohort and animal model studies that implicates sex differences in the developmental origins of cardiometabolic disease following exposure to maternal obesity and GDM. In addition, this review addresses the potential mechanisms involved in these sex differences. In many studies, sex is ignored as an important variable in disease development; however, the results presented in this review highlight important differences between sexes in the developmental programming of biological responses to exposures during the fetal stage. This knowledge will ultimately help in the development of effective therapeutic strategies for the treatment of cardiometabolic diseases that exhibit sexual dimorphism.

Salacia Chinensis Extract (SCE) Modulates Carbohydrates and Lipid Metabolism: in vitro and in vivo Models

Background: Salacia Chinensis (SC) is herbal medicine in Ayurvedic medicine. The extract of Salacia chinensis showed preventive effects on various metabolic health disorders. Objective: The aim of this study was to elucidate the therapeutic efficacy of the extract of Salacia chinensis extract (SCE) and modulation of carbohydrate and lipid metabolism in in vitro and in vivo models. Methods: In vitro studies were conducted to study the effect of Salacia chinensis extract (SCE, OmniLeanTM) on alpha-glucosidase, pancreatic lipase and HMG-CoA reductase. The activity of α-glucosidase was assessed using mammalian α-glucosidase extracted from rat intestinal acetone powder (Sigma) and p-nitrophenyl L-D glucopyranoside (PNPG) as an artificial substrate. Pancreatic lipase activity was assessed using pancreatic porcine lipase and 4-methylumbelliferyl oleate (MU Oleate) as substrate. Lipase activity was measured using a fluorescence kinetic assay. HMG-CoA reductase was the rate-limiting step in cholesterol synthesis. The activity of HMG-CoA reductase was assessed using HMG-CoA reductase assay kit (Sigma CS1090). Nutrigenomics study was conducted to study the effect of SCE on fatty acids, PPAR gamma and C/EBP α. In an in vivo model, fifty-six (56) male C57BL/6 mice were purchased from Charles River Labs, at the age of 5 weeks. The mice were housed individually in mouse cages in a temperature-controlled room with a 12-hour light and dark cycle and free access to regular rodent chow and water. After a week of adaptation, the mice were divided into 3 groups with 8 mice in each group. All mice were fed a high-fat diet (60% energy from fat) to induce obesity. One of the group was administered with low (100mg/kg/d) and high (500mg/kg/d) doses of SCE suspending in 0.5% carboxymethyl cellulose, respectively for 7.5 weeks (52 days). One group was used as the obese control (N=24) and gavage with the vehicle control. Body weights were obtained daily and food intake was recorded thrice every week. Body weights and food intake were recorded thrice every week. Fecal samples were collected during week 6 and 7. Serum lipid analysis, glycerol, free fatty acids, hormonal assays (ghrelin, adiponectin, leptin, insulin, glucose and GLP), fecal crude lipids and histopathology changes were assessed. Results: Salacia chinensis extract (SCE) showed a significant inhibitory effect on α-glucosidase. SCE demonstrated a significant inhibitory effect against pancreatic lipase, compared to orlistat. SCE inhibited HMG-C0A only at higher concentration (1mg/ml). In nutrigenomics model, SCE upregulated C/EBP alpha and down regulated ACC, PPARG and SCD-1. SCE at the dose of 500mg/kg/d significantly slowed body weight gain, reduced food intake, increased adiponectin, decreased fat pads mass and increased fecal fat excretion in animal model. SCE significantly decreased significantly serum glycerol levels (by 69%) and free fatty acids levels (by 77%) compared to control group. Treatment with SCE decreased by 20% leptin levels and by 21% insulin levels and increases by 16% adiponectin but did not affect glucose or GLP-1 levels. Conclusions: In vitro results suggest the effects of SCE in modulating gastrointestinal carbohydrate and lipid digestion and absorption, may be advocated as a candidate for obesity-diabetes prevention and phytotherapy. Animal study (in vivo) results suggest the inhibition of fat absorption slows weight gain and reducing effects of metabolic risk factors with SCE. More experiments need to be performed to optimize the optimal concentration that has an effect in vivo on body weight or food intake.

Inferring causal relationships between reproductive and metabolic health disorders and production traits in first-lactation US Holsteins using recursive models

Health disorders in dairy cows have a substantial effect on the profitability of a dairy enterprise because of loss in milk sales, culling of unhealthy cows, and replacement costs. Complex relationships exist between health disorders and production traits. Understanding the causal structures among these traits may help us disentangle these complex relationships. The principal objective of this study was to use producer-recorded data to explore phenotypic and genetic relationships among reproductive and metabolic health disorders and production traits in first-lactation US Holsteins. A total of 77,004 first-lactation daughters’ records of 2,183 sires were analyzed using recursive models. Health data contained information on reproductive health disorders [retained placenta (RP); metritis (METR)] and metabolic health disorders [ketosis (KETO); displaced abomasum (DA)]. Production traits included mean milk yield (MY) from early lactation (mean MY from 6 to 60d in milk and from 61 to 120d in milk), peak milk yield (PMY), day in milk of peak milk yield (PeakD), and lactation persistency (LP). Three different sets of traits were analyzed in which recursive effects from each health disorder on culling, recursive effects of one health disorder on another health disorder and on MY, and recursive effects of each health disorder on production traits, including PeakD, PMY, and LP, were assumed. Different recursive Gaussian-threshold and threshold models were implemented in a Bayesian framework. Estimates of the structural coefficients obtained between health disorders and culling were positive; on the liability scale, the structural coefficients ranged from 0.929 to 1.590, confirming that the presence of a health disorder increased culling. Positive recursive effects of RP to METR (0.117) and of KETO to DA (0.122) were estimated, whereas recursive effects from health disorders to production traits were negligible in all cases. Heritability estimates of health disorders ranged from 0.023 to 0.114, in accordance with previous studies. Similarly, genetic correlations obtained between health disorders were moderate. The results obtained suggest that reproductive and metabolic health disorder and culling due to metabolic and reproductive diseases have strong causal relationships. Based on these results, we concluded that a health disorder (either reproductive or metabolic) occurring in early lactation has a moderate causal effect on the reproductive or metabolic health disorder occurring in later lactation. In addition, direct, indirect, and overall effects of reproductive and metabolic health disorders on milk yields for cows that avoid culling are weak.

Can hormones contained in mothers’ milk account for the beneficial effect of breast‐feeding on obesity in children?

Nutrition and growth during infancy are an emerging issue because of their potential link to metabolic health disorders in later life. Moreover, prolonged breast-feeding appears to be associated with a lower risk of obesity than formula feeding. Human milk is a source of various hormones and growth factors, namely adipokines (leptin and adiponectin), ghrelin, resistin and obestatin, which are involved in food intake regulation and energy balance. These compounds are either not found in commercial milk formulas or their presence is still controversial. Diet-related differences during infancy in serum levels of factors involved in energy metabolism might explain anthropometric differences and also differences in dietary habits between breast-fed (BF) and formula-fed (FF) infants later in life, and may thus have long-term health consequences. In this context, the recent finding of higher leptin levels and lower ghrelin levels in BF than in FF infants suggests that differences in hormonal values together with different protein intake could account for the differences in growth between BF and FF infants both during infancy and later in life. In this review, we examine the data related to hormones contained in mothers' milk and their potential protective effect on subsequent obesity and metabolic-related disorders.