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Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept.
Kim, DH, Bang, E, Jung, HJ, Noh, SG, Yu, BP, Choi, YJ, Chung, HY
Nutrients. 2020;12(2)
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Low grade, systemic, chronic inflammation is a feature of ageing and underlies many age-related chronic diseases states. As cells age their capacity to proliferate declines, which is referred to as cell senescence. Such senescent cells release multiple inflammatory markers contributing to a pro-inflammatory state. This is further aggravated by elevated oxidative stress and a reduced capacity to manage it, eventually leading to improper gene regulation and DNA damage. To define this age-related, complex inflammatory phenomena the authors introduced the term senoinflammation. A well-established intervention to reverse or slow down the ageing process and many ageing-associated diseases is calorie restriction (CR), by means of reducing overall caloric intake without malnutrition. CR exhibits potent anti-inflammatory effects, reduces age-associated oxidative stress, improves age-related metabolic dysregulation and enhances favourable gene expression. This review summarises how CR and CR-mimicking substances exert their anti-inflammatory effect and some of the cellular mechanism involved and may be of interest to those who are looking to get a more detailed understanding on ageing, inflammation and the benefits of CR.
Abstract
Chronic inflammation, a pervasive feature of the aging process, is defined by a continuous, multifarious, low-grade inflammatory response. It is a sustained and systemic phenomenon that aggravates aging and can lead to age-related chronic diseases. In recent years, our understanding of age-related chronic inflammation has advanced through a large number of investigations on aging and calorie restriction (CR). A broader view of age-related inflammation is the concept of senoinflammation, which has an outlook beyond the traditional view, as proposed in our previous work. In this review, we discuss the effects of CR on multiple phases of proinflammatory networks and inflammatory signaling pathways to elucidate the basic mechanism underlying aging. Based on studies on senoinflammation and CR, we recognized that senescence-associated secretory phenotype (SASP), which mainly comprises cytokines and chemokines, was significantly increased during aging, whereas it was suppressed during CR. Further, we recognized that cellular metabolic pathways were also dysregulated in aging; however, CR mimetics reversed these effects. These results further support and enhance our understanding of the novel concept of senoinflammation, which is related to the metabolic changes that occur in the aging process. Furthermore, a thorough elucidation of the effect of CR on senoinflammation will reveal key insights and allow possible interventions in aging mechanisms, thus contributing to the development of new therapies focused on improving health and longevity.
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A cross-sectional study: Associations between sarcopenia and clinical characteristics of patients with type 2 diabetes.
Cui, M, Gang, X, Wang, G, Xiao, X, Li, Z, Jiang, Z, Wang, G
Medicine. 2020;99(2):e18708
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Sarcopenia is characterised by the loss of muscle mass, decrease of muscle strength and decline of physical performance and is related to reduced physical ability, impaired cardiorespiratory function, disability and death in the elderly. Type 2 diabetics are at higher risk of developing sarcopenia. The aim of this cross-sectional study was to evaluate clinical characteristics of sarcopenia in elderly type 2 diabetics in the Northeast of China. 132 participants completed the study which was based on self-reported medical and lifestyle history, and clinical evaluations including measurements of weight, height and muscle strength, imaging to establish sarcopenia and blood tests. 28.8% of participants had sarcopenia. Age, increased truncal fat mass and increased free thyroxine increased the risk of sarcopenia, whilst regular exercise, being female, taking metformin, a higher body mass index and increased trunk skeletal mass were associated with a lower risk of sarcopenia. The authors point out that limitations include the small sample size and that, as this is a cross-sectional study, cause and effect cannot be established.
Abstract
Sarcopenia is a geriatric syndrome and it impairs physical function. Patients with type 2 diabetes mellitus (T2DM) are at a higher risk of sarcopenia. The purpose of this study is to explore characteristics of general information and metabolic factors of sarcopenia in patients with T2DM in the northeast of China, and provide information for the prevention and treatment of sarcopenia in clinical practice.Patients with T2DM aged ≥65 were recruited in Changchun from March 2017 to February 2018. Questionnaires of general information, physical examination, laboratory and imaging examination were conducted. The patients were assigned into sarcopenia group and non-sarcopenia group according to the diagnostic criteria proposed by Asian working group for sarcopenia (AWGS), and the differences between 2 groups were analyzed.A total of 132 participants were included in this study, of which, 38 (28.8%) were diagnosed with sarcopenia. 94 (71.2%) were with no sarcopenia. Logistic regression analysis showed that age (OR: 1.182, 95%CI: 1.038-1.346), trunk fat mass (TFM) (OR: 1.499, 95%CI: 1.146-1.960) and free thyroxine (FT4) (OR: 1.342, 95%CI: 1.102-1.635) were independent risk factors for sarcopenia. BMI (body mass index) (OR: 0.365, 95%CI: 0.236-0.661), exercise (OR: 0.016, 95%CI: 0.001-0.169), female (OR: 0.000, 95%CI: 0.00-0.012), metformin (OR: 0.159, 95%CI: 0.026-0.967) and TSM (trunk skeletal muscle mass) (OR: 0.395, 95%CI: 0.236-0.661) were protective factors for sarcopenia.Sarcopenia in patients with T2DM is associated with increased age, increased TFM and increased FT4 level. Regular exercise, female, metformin administrations, high BMI and increased TSM are associated with lower risk of sarcopenia.
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Clinical Impact of Supplementation of Vitamins B1 and C on Patients with Sepsis-Related Acute Respiratory Distress Syndrome.
Yoo, JW, Kim, RB, Ju, S, Lee, SJ, Cho, YJ, Jeong, YY, Lee, JD, Kim, HC
Tuberculosis and respiratory diseases. 2020;83(3):248-254
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Acute respiratory distress syndrome (ARDS) is a life-threatening condition that commonly develops in patients with sepsis. Patients with ARDS require admission to intensive care and invasive mechanical ventilation. Vitamin B1 and C deficiencies have been reported in critically ill patients with sepsis. Vitamin B1 is involved in aerobic metabolism, and vitamin C has anti-inflammatory and anti-oxidative effects. The aim of this Korean retrospective cohort study was to evaluate the clinical impact of vitamin B1 and C supplementation in patients with sepsis-related ARDS. Patients with ARDS requiring invasive mechanical ventilation, admitted to an intensive care unit (ICU) were included in this study. Clinical outcomes were compared between patients administered with vitamin B1 (200 mg/day) and C (2 g/day) between June 2018-May 2019 (the supplementation group) and those who did not receive vitamin B1 and C administration between June 2017-May 2018 (the control group). Seventy-nine patients were included. Thirty-three patients received vitamin B1 and C, and 46 patients did not. There were no significant differences in the number of deaths between the patients who received vitamin B1 and C and those who did not. The mean number of days not requiring ICU admission or ventilation was greater in patients supplemented with vitamin B1 and C than that in the control patients, but the difference was not statistically significant. Steroid administration was more frequent in patients receiving vitamin B1 and C supplementation than in those without it. The authors concluded that Vitamin B1 and C supplementation at the doses used in this study did not reduce the death rates in ARDS patients.
Abstract
BACKGROUND Although few studies have reported improved clinical outcomes with the administration of vitamin B1 and C in critically ill patients with septic shock or severe pneumonia, its clinical impact on patients with sepsis-related acute respiratory distress syndrome (ARDS) remains unclear. The purpose of this study was to evaluate the association with vitamin B and C supplementation and clinical outcomes in patients with ARDS. METHODS Patients with ARDS requiring invasive mechanical ventilation, admitted to the medical intensive care unit (ICU) were included in this study. Clinical outcomes were compared between patients administered with vitamin B1 (200 mg/day) and C (2 g/day) June 2018-May 2019 (the supplementation group) and those who did not receive vitamin B1 and C administration June 2017-May 2018 (the control group). RESULTS Seventy-nine patients were included. Thirty-three patients received vitamin B1 and C whereas 46 patients did not. Steroid administration was more frequent in patients receiving vitamin B1 and C supplementation than in those without it. There were no significant differences in the mortality between the patients who received vitamin B1 and C and those who did not. There were not significant differences in ventilator and ICU-free days between each of the 21 matched patients. CONCLUSION Vitamin B1 and C supplementation was not associated with reduced mortality rates, and ventilator and ICU-free days in patients with sepsis-related ARDS requiring invasive mechanical ventilation.
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Endocrine and metabolic aspects of the COVID-19 pandemic.
Marazuela, M, Giustina, A, Puig-Domingo, M
Reviews in endocrine & metabolic disorders. 2020;21(4):495-507
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Endocrine and metabolic related diseases such as diabetes and obesity may increase the risk of developing severe Covid-19 and as a result these diseases could be severely affected by Covid-19 infection. This very large review paper looked at over 100 studies and outlined the interrelationship between Covid-19 infection and several endocrine diseases. Diabetes, obesity, pituitary-hypothalamic function, thyroid function, Cushing's syndrome and adrenal function were all reviewed. No aim was stated. Data on individuals with obesity and diabetes indicated an increased risk for severe Covid-19 infection, hospitalisation and mortality. Data surrounding pituitary-hypothalamic function, thyroid function, Cushing's syndrome and adrenal function was less abundant, however neurological issues in Covid-19 patients suggested an involvement of the pituitary and hypothalamus. In lieu of sufficient data the author commented on the possible similarities between severe acute respiratory syndrome coronavirus with the Covid-19 virus. A number of management strategies were discussed such as the use of vitamin D, oxytocin and melatonin, however the authors commented on the lack of data regarding oxytocin and melatonin in Covid-19 patients, but mechanistic data suggested they might be of use. No overall conclusions were drawn on the findings. Clinicians could use this paper to understand how patients with pre-existing endocrine and metabolic conditions may be at a higher risk of more severe Covid-19 and if contracted could exacerbate their pre-existing condition. These patients could require constant monitoring and additional measures to avoid contracting Covid-19. Supplements such as vitamin D, oxytocin or melatonin could be therapeutic, however more data needs to be reviewed.
Abstract
COVID-19 infection has tremendously impacted our daily clinical practice as well as our social living organization. Virtually all organs and biological systems suffer from this new coronavirus infection, either because the virus targets directly specific tissues or because of indirect effects. Endocrine diseases are not an exception and some of endocrine organs are at risk of direct or indirect lesion by COVID-19. Although there is still no evidence of higher predisposition to contract the infection in patients with diabetes and/or obesity, the coexistence of these conditions contributes to a worse prognosis because both conditions confer an impaired immunologic system. Cytokines storm can be amplified by these two latter conditions thereby leading to multisystemic failure and death. Glycaemic control has been demonstrated to be crucial to avoiding long hospital stays, ICU requirement and also prevention of excessive mortality. Endocrine treatment modifications as a consequence of COVID-19 infection are required in a proactive manner, in order to avoid decompensation and eventual hospital admission. This is the case of diabetes and adrenal insufficiency in which prompt increase of insulin dosage and substitutive adrenal steroids through adoption of the sick day's rules should be warranted, as well as easy contact with the health care provider through telematic different modalities. New possible endocrinological targets of COVID-19 have been recently described and warrant a full study in the next future.
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The Effect of Moderate Weight Loss on a Non-Invasive Biomarker of Liver Fibrosis: A Randomised Controlled Trial.
Koutoukidis, DA, Jebb, SA, Aveyard, P, Astbury, NM
Obesity facts. 2020;13(2):144-151
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Non-alcoholic fatty liver disease covers a range of conditions from excess fat in the liver through inflammation and fibrosis, to advanced fibrosis, and cirrhosis. The Enhanced Liver Fibrosis (ELF) score is emerging as a promising blood biomarker for fibrosis. The aim of this study was to examine whether a community weight loss programme reduces ELF score over 12 months compared with a weight-loss intervention which is less effective. This study is a secondary analysis of a published randomised controlled trial. Participants (n=73) were equally randomised to a community weight loss programme (WeightWatchers) or usual care. Results indicate that there was no evidence of an effect of a community weight loss programme on changes in the ELF score and no association between weight loss and the ELF score in people who had, on average, an ELF score compatible with moderate fibrosis. Authors conclude that using the ELF test to assess weight loss treatment efficacy in improving liver fibrosis may be of limited value, thus biopsy remains the gold-standard assessment for liver fibrosis.
Abstract
BACKGROUND Referral to weight loss programmes is the only effective treatment for non-alcoholic fatty liver disease (NAFLD). Clinicians should advise weight loss and screen for liver fibrosis using the Enhanced Liver Fibrosis (ELF) score. AIM: To examine if the ELF score changes with weight loss. DESIGN AND SETTING Randomised controlled trial (ISRCTN85485463) in UK primary care during 2007-2008. METHOD Adults with a BMI of 27-35 kg/m2 and ≥1 risk factor for obesity-related disease were randomised to attend a community weight loss programme (n = 45) or receive usual weight loss advice from a practice nurse (n = 28). Weight and the ELF score were measured at baseline and 1 year. Analysis of covariance examined mean changes in the ELF score between groups and its relationship with weight loss. RESULTS Mean (SD) BMI was 31.10 kg/m2 (2.55) with evidence of moderate levels of liver fibrosis at baseline (mean ELF score: 8.93 [0.99]). There was no evidence that the community weight loss programme reduced the ELF score compared with usual care (difference +0.13 points, 95% CI: -0.25 to 0.52) despite greater weight loss (difference: -2.66 kg, 95% CI: -5.02 to -0.30). Mean weight loss in the whole cohort was 7.8% (5.9). There was no evidence of an association between weight change and change in ELF; the coefficient for a 5% weight loss was -0.15 (95% CI: -0.30 to 0.0002). CONCLUSION We found no evidence that the ELF score changed meaningfully following moderate weight loss. Clinicians should not use the ELF score to measure improvements in NAFLD fibrosis following weight loss programmes.
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Effect of Smartphone-Based Lifestyle Coaching App on Community-Dwelling Population With Moderate Metabolic Abnormalities: Randomized Controlled Trial.
Cho, SMJ, Lee, JH, Shim, JS, Yeom, H, Lee, SJ, Jeon, YW, Kim, HC
Journal of medical Internet research. 2020;22(10):e17435
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Metabolic disorders are established precursors to cardiovascular disease. The aim of the study was to evaluate the longitudinal effect of smartphone-based health care app on metabolic parameters in a sample of the general population with moderate metabolic abnormalities. The study is a single-blind 3-arm parallel-design randomized controlled trial delivering a 6-month primary prevention program via mobile app. One hundred twenty-nine smartphone users, aged between 30-59 years with at least 2 metabolic abnormalities, have been recruited. Results showed that the simultaneous diet/exercise logging and lifestyle coaching yielded greater body weight reduction, specifically via body fat mass reduction. On the other hand, the systolic blood pressure did not change notably between the 3 groups at any follow-up examinations. Authors conclude that future studies focusing on comparative effectiveness using alternative study designs are needed to integrate these apps in everyday lives and clinic practice.
Abstract
BACKGROUND Metabolic disorders are established precursors to cardiovascular diseases, yet they can be readily prevented with sustained lifestyle modifications. OBJECTIVE We assessed the effectiveness of a smartphone-based weight management app on metabolic parameters in adults at high-risk, yet without physician diagnosis nor pharmacological treatment for metabolic syndrome, in a community setting. METHODS In this 3-arm parallel-group, single-blind, randomized controlled trial, we recruited participants aged 30 to 59 years with at least 2 conditions defined by the Third Report of the National Cholesterol Education Program expert panel (abdominal obesity, high blood pressure, high triglycerides, low high-density lipoprotein cholesterol, and high fasting glucose level). Participants were randomly assigned (1:1:1) by block randomization to either the nonuser group (control), the app-based diet and exercise self-logging group (app only), or the app-based self-logging and personalized coaching from professional dieticians and exercise coordinators group (app with personalized coaching). Assessments were performed at baseline, week 6, week 12, and week 24. The primary outcome was change in systolic blood pressure (between baseline and follow-up assessments). Secondary outcomes were changes in diastolic blood pressure, body weight, body fat mass, waist circumference, homeostatic model of assessment of insulin resistance, triglyceride level, and high-density lipoprotein cholesterol level between baseline and follow-up assessments. Analysis was performed using intention-to-treat. RESULTS Between October 28, 2017 and May 28, 2018, 160 participants participated in the baseline screening examination. Participants (129/160, 80.6%) who satisfied the eligibility criteria were assigned to control (n=41), app only (n=45), or app with personalized coaching (n=43) group. In each group, systolic blood pressure showed decreasing trends from baseline (control: mean -10.95, SD 2.09 mmHg; app only: mean -7.29, SD 1.83 mmHg; app with personalized coaching: mean -7.19, SD 1.66 mmHg), yet without significant difference among the groups (app only: P=.19; app with personalized coaching: P=.16). Instead, those in the app with personalized coaching group had greater body weight reductions (control: mean -0.12, SD 0.30 kg; app only: mean -0.35, SD 0.36 kg, P=.67; app with personalized coaching: mean -0.96, SD 0.37 kg; P=.08), specifically by body fat mass reduction (control: mean -0.13, SD 0.34 kg; app only: mean -0.64, SD 0.38 kg, P=.22; app with personalized coaching: mean -0.79, SD 0.38 kg; P=.08). CONCLUSIONS Simultaneous diet and exercise self-logging and persistent lifestyle modification coaching were ineffective in lowering systolic blood pressure but effective in losing weight and reducing body fat mass. These results warrant future implementation studies of similar models of care on a broader scale in the context of primary prevention. TRIAL REGISTRATION ClinicalTrials.gov NCT03300271; http://clinicaltrials.gov/ct2/show/NCT03300271.
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Stratifying cellular metabolism during weight loss: an interplay of metabolism, metabolic flexibility and inflammation.
Tareen, SHK, Kutmon, M, de Kok, TM, Mariman, ECM, van Baak, MA, Evelo, CT, Adriaens, ME, Arts, ICW
Scientific reports. 2020;10(1):1651
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Obesity is a public health concern as it has been linked to cardiovascular diseases, type 2 diabetes and metabolic syndrome. The aim of this study was to identify and analyse expression profiles of individuals clustered by cellular metabolism centring on metabolic flexibility. This study clustered gene expression samples from a weight loss study (Yoyo study’ - Clinical Trial ID: NCT01559415) into two clusters, based on 291 genes associated with cellular metabolic fexibility. The study covers two diets: a low-calorie diet (LCD) and a very low-calorie diet (VLCD). All the participants of the study were Caucasian with a BMI between 28kg/m2 and 35 kg/m2, aged between 32 and 67 years old. Findings showed that the majority of the individuals had their metabolism associated genes downregulated after weight loss and weight maintenance, but also had an upregulation of immune system associated genes. Furthermore, individuals who had changed their metabolic profiles in response to caloric restriction had a significant retention of lost weight compared to individuals which had not changed their cluster membership. Authors conclude that their findings indicate possible cross-talk between cellular metabolism and inflammation.
Abstract
Obesity is a global epidemic, contributing significantly to chronic non-communicable diseases, such as type 2 diabetes mellitus, cardiovascular diseases and metabolic syndrome. Metabolic flexibility, the ability of organisms to switch between metabolic substrates, is found to be impaired in obesity, possibly contributing to the development of chronic illnesses. Several studies have shown the improvement of metabolic flexibility after weight loss. In this study, we have mapped the cellular metabolism of the adipose tissue from a weight loss study to stratify the cellular metabolic processes and metabolic flexibility during weight loss. We have found that for a majority of the individuals, cellular metabolism was downregulated during weight loss, with gene expression of all major cellular metabolic processes (such as glycolysis, fatty acid β-oxidation etc.) being lowered during weight loss and weight maintenance. Parallel to this, the gene expression of immune system related processes involving interferons and interleukins increased. Previously, studies have indicated both negative and positive effects of post-weight loss inflammation in the adipose tissue with regards to weight loss or obesity and its co-morbidities; however, mechanistic links need to be constructed in order to determine the effects further. Our study contributes towards this goal by mapping the changes in gene expression across the weight loss study and indicates possible cross-talk between cellular metabolism and inflammation.
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Effects of Synbiotic Supplement on Human Gut Microbiota, Body Composition and Weight Loss in Obesity.
Sergeev, IN, Aljutaily, T, Walton, G, Huarte, E
Nutrients. 2020;12(1)
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The gut microbiota plays a role in the development of obesity and associated diseases. Whilst energy-restricted, low-carbohydrate, high-protein diets can facilitate substantial weight-loss, they also have been linked to ill-effects and unfavourable changes in the gut microbiota from excess protein fermentation. Pro-and prebiotics (synbiotics) have become a promising intervention in the management of obesity. This small placebo-controlled clinical trial involved 20 obese adults following an energy-restricted (approx.950 kcal/day) low-carbohydrate, high-protein diet. The study examined whether a supplementary synbiotic contributed to additional changes in body composition and metabolic biomarkers. The synbiotic contained Lactobacilli spp. and Bifidobacteria spp. and a prebiotic mixture of galactooligosaccharides. Overall, at the end of the 3-month trial, there was no remarkable difference between the groups. Both experienced a significant and decreasing trend in body mass, waist circumference, body mass index, fat mass, fat percentage, and glucose level, affirming the known benefits of the described weight-loss diet. However, the synbiotic supplementation group had a greater decrease in HbA1C and significant alterations in gut microbiota, showing an increased abundance of gut bacteria associated with positive health effects. Due to the complexity of microbial species and host interactions, the authors advocate for more research to identify their significance and shed light on contradictory findings. This study identified that synbiotics may not contribute to additional changes in body composition when combined with an energy-restricted, low-carbohydrate, high-protein diet but they can offer additional health benefits by inducing favourable changes to the gut microbiota.
Abstract
Targeting gut microbiota with synbiotics (probiotic supplements containing prebiotic components) is emerging as a promising intervention in the comprehensive nutritional approach to reducing obesity. Weight loss resulting from low-carbohydrate high-protein diets can be significant but has also been linked to potentially negative health effects due to increased bacterial fermentation of undigested protein within the colon and subsequent changes in gut microbiota composition. Correcting obesity-induced disruption of gut microbiota with synbiotics can be more effective than supplementation with probiotics alone because prebiotic components of synbiotics support the growth and survival of positive bacteria therein. The purpose of this placebo-controlled intervention clinical trial was to evaluate the effects of a synbiotic supplement on the composition, richness and diversity of gut microbiota and associations of microbial species with body composition parameters and biomarkers of obesity in human subjects participating in a weight loss program. The probiotic component of the synbiotic used in the study contained Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium longum, and Bifidobacterium bifidum and the prebiotic component was a galactooligosaccharide mixture. The results showed no statistically significant differences in body composition (body mass, BMI, body fat mass, body fat percentage, body lean mass, and bone mineral content) between the placebo and synbiotic groups at the end of the clinical trial (3-month intervention, 20 human subjects participating in weight loss intervention based on a low-carbohydrate, high-protein, reduced energy diet). Synbiotic supplementation increased the abundance of gut bacteria associated with positive health effects, especially Bifidobacterium and Lactobacillus, and it also appeared to increase the gut microbiota richness. A decreasing trend in the gut microbiota diversity in the placebo and synbiotic groups was observed at the end of trial, which may imply the effect of the high-protein low-carbohydrate diet used in the weight loss program. Regression analysis performed to correlate abundance of species following supplementation with body composition parameters and biomarkers of obesity found an association between a decrease over time in blood glucose and an increase in Lactobacillus abundance, particularly in the synbiotic group. However, the decrease over time in body mass, BMI, waist circumstance, and body fat mass was associated with a decrease in Bifidobacterium abundance. The results obtained support the conclusion that synbiotic supplement used in this clinical trial modulates human gut microbiota by increasing abundance of potentially beneficial microbial species.
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Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus.
Stomby, A, Otten, J, Ryberg, M, Andrew, R, Walker, BR, Olsson, T
European journal of endocrinology. 2020;182(4):447-457
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Cushing syndrome is caused by an overexposure to cortisol and associated with abdominal adiposity, hypertension, dyslipidaemia, insulin resistance and type 2 diabetes mellitus (T2DM), and therefore bears similarities with metabolic syndrome and obesity. Whilst circulating cortisol levels are normal or slightly decreased in obese individuals, they tend to be increased in T2DM. The aim of this study was to investigate associations between obesity and T2DM measures and glucocorticoid metabolism, and any possible effects of a palaeolithic diet (PD) with or without exercise. In this single-blind study (investigators examining patients were blind to intervention), 28 patients with overweight or obesity and T2DM were randomised to either a PD alone or combined with a structured resistance and aerobic exercise programme for 12 weeks. The PD was based on a high intake of vegetables, fruit, lean meat, nuts, egg, fish and seafood, whilst grains, sugar, salt, dairy products and refined fats were reduced. Body mass index, waist circumference, glycaemic control, liver and systemic insulin sensitivity improved in both groups with no statistically significant difference between groups. There was no association between insulin sensitivity and indices of tissue specific glucocorticoid metabolism. PD with and without exercise was associated with increased conversion of the inactive cortisone to the active cortisol through increased activity of the conversion enzyme in the liver, but not with increased urinary excretion of glucocorticoid metabolites. The authors concluded that the results suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.
Abstract
CONTEXT Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. OBJECTIVE Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. DESIGN Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). SETTING Umeå University Hospital. PARTICIPANTS Men and women with type 2 diabetes treated with lifestyle modification ± metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. MAIN OUTCOME MEASURES Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD11B1 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. RESULTS Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5α-THF + 5β-THF/THE in urine increased in both groups. CONCLUSIONS These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.
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You Are What You Eat-The Relationship between Diet, Microbiota, and Metabolic Disorders-A Review.
Moszak, M, Szulińska, M, Bogdański, P
Nutrients. 2020;12(4)
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The gut microbiota (GM) is a collection of microorganisms living in the digestive tract of humans, which if unbalanced, may have a role in the development of certain disorders such as type 2 diabetes and obesity. A number of factors can imbalance the gut microbiota, one of the main being diet. This review paper of 190 papers aimed to summarise the relationship between GM, diet and modifiable diseases such as type 2 diabetes and obesity. Dietary components and the role of carbohydrates, protein and fats in shaping the GM were discussed. It was determined that carbohydrates have the greatest influence, with simple carbohydrates such as the sugars fructose and sucrose having a negative impact and the more complex forms being beneficial. Diet types were also reviewed. Vegetarian and vegan diets appear to increase the diversity of the GM, the Mediterranean diet changes the species balance, and the Western diet imbalances the GM causing diseases such as heart disease. Interestingly the literature points towards a negative impact of the gluten free diet. Diseases such as type 2 diabetes, obesity and increased fats in the blood all display an imbalanced GM causing increased energy harvest from food and disruption of various energy pathways in the body. It was concluded that a balanced diet rich in fruit, vegetables, fibre and healthy fats can promote GM diversity and activity. This study could be used by health care professionals to understand the importance of certain dietary components to promote GM diversity in order to reduce the risk of diseases such as obesity and type 2 diabetes.
Abstract
The gut microbiota (GM) is defined as the community of microorganisms (bacteria, archaea, fungi, viruses) colonizing the gastrointestinal tract. GM regulates various metabolic pathways in the host, including those involved in energy homeostasis, glucose and lipid metabolism, and bile acid metabolism. The relationship between alterations in intestinal microbiota and diseases associated with civilization is well documented. GM dysbiosis is involved in the pathogenesis of diverse diseases, such as metabolic syndrome, cardiovascular diseases, celiac disease, inflammatory bowel disease, and neurological disorders. Multiple factors modulate the composition of the microbiota and how it physically functions, but one of the major factors triggering GM establishment is diet. In this paper, we reviewed the current knowledge about the relationship between nutrition, gut microbiota, and host metabolic status. We described how macronutrients (proteins, carbohydrates, fat) and different dietary patterns (e.g., Western-style diet, vegetarian diet, Mediterranean diet) interact with the composition and activity of GM, and how gut bacterial dysbiosis has an influence on metabolic disorders, such as obesity, type 2 diabetes, and hyperlipidemia.