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Coping Strategies Influence Cardiometabolic Risk Factors in Chronic Psychological Stress: A Post Hoc Analysis of A Randomized Pilot Study.
Armborst, D, Bitterlich, N, Alteheld, B, Rösler, D, Metzner, C, Siener, R
Nutrients. 2021;14(1)
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Chronic psychological stress is increasingly recognized as a significant contributor to mental and physiological disorders in modern societies. The individual response to chronic stressors and resulting disorders depends on numerous factors. The aim of this study was to investigate the cardiometabolic risk profile in participants with ‘high’ and ‘very high’ chronic stress loads and the impact of positive and negative coping factors used. This study is a post hoc analysis of a randomised pilot study. For this analysis, baseline data were available for 62 chronic psychologically stressed participants, of whom 61 participants (43 women and 18 men) were included in the intention-to-treat (ITT) population. Results indicate that: - perceiving high chronic stress is significantly associated with the criteria of the metabolic syndrome. - on the contrary, a very high perceived chronic stress load seemed to be rather associated with mental health risk than with cardiometabolic risk. - inflammation and oxidative stress markers significantly correlated with cardiometabolic risk parameters. - stress load can be coped with in diverse ways and that the coping strategy is crucial for cardiometabolic risk. Authors conclude that long-term studies are necessary to examine further adaptations to chronic stress and to evaluate individual stress-management strategies.
Abstract
Chronic psychological stress can result in physiological and mental health risks via the activation of the hypothalamic-pituitary-adrenal (HPA) axis, sympathoadrenal activity and emotion-focused coping strategies. The impact of different stress loads on cardiometabolic risk is poorly understood. This post hoc analysis of a randomized pilot study was conducted on 61 participants (18-65 years of age) with perceived chronic stress. The Perceived Stress Questionnaire (PSQ30), Psychological Neurological Questionnaire (PNF), anthropometric, clinical and blood parameters were assessed. Subjects were assigned to 'high stress' (HS; PSQ30 score: 0.573 ± 0.057) and 'very high stress' (VHS; PSQ30 score: 0.771 ± 0.069) groups based on the PSQ30. Morning salivary cortisol and CRP were elevated in both groups. Visceral adiposity, elevated blood pressure and metabolic syndrome were significantly more frequent in the HS group vs. the VHS group. The fatty liver index (FLI) was higher (p = 0.045), while the PNF score was lower (p < 0.001) in the HS group. The HS group was comprised of more smokers (p = 0.016). Energy intake and physical activity levels were similar in both groups. Thus, high chronic stress was related to visceral adiposity, FLI, elevated blood pressure and metabolic syndrome in the HS group, while very high chronic stress was associated with psychological-neurological symptoms and a lower cardiometabolic risk in the VHS group, probably due to different coping strategies.
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Type 2 diabetes preventive effects with a 12-months sardine-enriched diet in elderly population with prediabetes: An interventional, randomized and controlled trial.
Díaz-Rizzolo, DA, Serra, A, Colungo, C, Sala-Vila, A, Sisó-Almirall, A, Gomis, R
Clinical nutrition (Edinburgh, Scotland). 2021;40(5):2587-2598
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Older people have a higher risk of developing Type 2 diabetes (T2D) due to the possibility of β-cell dysfunction due to ageing. Sardines are believed to be protective against the development of T2D. Therefore, this randomised controlled trial evaluated the preventative effects of a sardine-rich diet in elderly prediabetic patients. For one year, both the sardine group (SG) and control group (CG) followed a T2D prevention diet, with the SG consuming 200 g of sardines each week. Both groups improved body weight, BMI, waist and hip circumference, and body composition. Taurine, EPA, DHA, omega-3 fatty acid, calcium, iodine, zinc, phosphorous and fluoride, vitamin B12 and D, and lycopene and tocopherols were found to be higher in the SG than the CG, indicating the sardines were protective against T2D. In SG, HDL cholesterol and adiponectin levels were significantly increased, and blood pressure and triglycerides were decreased, signalling a reduced risk of T2D and cardiovascular disease. In addition, SG showed a reduction in HOMA-IR and an Omega-3 fatty acid was substituted for Omega-6 fatty acids in the erythrocyte membrane, suggesting a reduced risk of T2D. Further robust research is required to confirm the protective effect of a sardine-enriched diet against T2D. It may be useful to healthcare providers to comprehend how a sardine-enriched diet could improve obesity, T2D and CVD markers in pre-diabetic elderly patients.
Abstract
BACKGROUND Fish could play a role in preventing type 2 diabetes (T2D) but there has been little specification about the type of fish and the preventive mechanism involved in its health claim. The sardine is a source of omega-3 and taurine that, in isolation or in synergy, would produce T2D-delaying through different molecular mechanism. HYPOTHESIS The consumption of twice a week of sardine, during one year would reduce T2D-developing risk in a population with prediabetes (preDM) and old age. DESIGN 152 subjects with fasting glucose between 100-124 mg/dL aged ≥65 yo were recruited from three primary care centers in Barcelona and were randomly distributed among two interventional groups: control group (CG) and sardine group (SG). Both groups received same T2D-prevention nutritional during a year but only SG had to add 200 g of sardine per week. All variables were collected before to start and at the end of the diet. (ClinicalTrials.gov: NCT03557541). RESULTS 152 people were randomized into CG (n=77) and SG (n=75) with 18 and 12 drop outs respectively. Subjects in SG, significantly compared to CG, decreased percentage classified-individuals in a very high risk group to develop T2D according to FINDRISC (p=0.035). In addition to increasing HDL-cholesterol and adiponectin and decreasing triglycerides (p<0.05) and blood pressure (<0.05), SG showed a lower HOMA-IR (p=0.032). The consumption of sardine characteristics nutrients as omega-3, EPA and DHA, vitamin D, fluorine and taurine were higher for SG (p<0.05). These results agreed with the increased of taurine, fatty acid (FA) omega-3 and bile acids circulating metabolites (p<0.05). Changes erythrocyte membrane FA were detected only in SG with a decrease of 5 omega-6 FA (p<0.001) and an increase of 3 omega-3 FA types (p<0.001). CONCLUSION We conclude that a year T2D-prevention diet with sardine supplementation has a greater protective effect against developing T2D and CV events.
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Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial.
Sabico, S, Enani, MA, Sheshah, E, Aljohani, NJ, Aldisi, DA, Alotaibi, NH, Alshingetti, N, Alomar, SY, Alnaami, AM, Amer, OE, et al
Nutrients. 2021;13(7)
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A highly contagious virus called SARS-CoV-2 is responsible for the Covid-19 pandemic. Vitamin D adjuvant therapy has been identified as a promising strategy for reducing the severity of Covid-19 outcomes in the elderly. Also, a low Vitamin D status significantly correlates with Covid-19 severity. This multi-centre randomised, open-label clinical trial evaluated the beneficial effects of 5000 IU versus 1000 IU Vitamin D3 daily supplementation for two weeks on recovery of symptoms in patients with mild-to-moderate Covid-19 and suboptimal Vitamin D status. Thirty-six Covid-19 patients received 5000 IU Vitamin D3 daily, and thirty-three Covid-19 patients received 1000 IU Vitamin D3 daily. The 5000 IU Vitamin D3 group was significantly younger and had a significantly lower BMI than the 1000 IU Vitamin D3 group. The 5000 IU Vitamin D3 group showed significant improvements in the severity of the Covid-19 symptoms compared to the 1000 IU Vitamin D3 group. Further robust studies are needed to evaluate the effects of Vitamin D3 supplementation in patients with high BMI, severe Covid-19 symptoms, and prevention of Covid-19. Healthcare professionals can use the results of this study to understand the effects of different doses of Vitamin D3 supplements in patients with mild-to-moderate Covid-19 symptoms and suboptimal Vitamin D status.
Abstract
OBJECTIVE Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. STUDY DESIGN AND SETTING A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. RESULTS Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). CONCLUSION A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.
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Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank.
Raisi-Estabragh, Z, McCracken, C, Bethell, MS, Cooper, J, Cooper, C, Caulfield, MJ, Munroe, PB, Harvey, NC, Petersen, SE
Journal of public health (Oxford, England). 2020;42(3):451-460
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The coronavirus disease 2019 (COVID-19) pandemic has to date resulted in over 6 million cases. Growing reports highlight men and Black, Asian and Minority Ethnic (BAME) cohorts as at higher risk of adverse COVID-19 outcomes. The aim of this study was to investigate whether differential patterns of COVID-19 incidence and severity, by sex and ethnicity, might be explained by cardiometabolic, socio-economic, lifestyle and behavioural exposures. This study is a prospective cohort study of over half a million men and women from across the UK. Results showed that male sex, BAME ethnicity, higher body mass index and greater household size were associated with significantly greater odds of a positive result. However, the sex and ethnicity differential pattern of COVID-19 is not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels, socio-economic or behavioural factors. Authors conclude that investigation of alternative biological and genetic susceptibilities as well as more comprehensive assessment of the complex economic, social and behavioural differences should be prioritised.
Abstract
BACKGROUND We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and Black, Asian and Minority Ethnic (BAME) individuals is explained by cardiometabolic, socio-economic or behavioural factors. METHODS We studied 4510 UK Biobank participants tested for COVID-19 (positive, n = 1326). Multivariate logistic regression models including age, sex and ethnicity were used to test whether addition of (1) cardiometabolic factors [diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking and body mass index (BMI)]; (2) 25(OH)-vitamin D; (3) poor diet; (4) Townsend deprivation score; (5) housing (home type, overcrowding) or (6) behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status. RESULTS There was over-representation of men and BAME ethnicities in the COVID-19 positive group. BAME individuals had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and in flats/apartments. Male sex, BAME ethnicity, higher BMI, higher Townsend deprivation score and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations. CONCLUSIONS In this study, sex and ethnicity differential pattern of COVID-19 was not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels or socio-economic factors. Factors which underlie ethnic differences in COVID-19 may not be easily captured, and so investigation of alternative biological and genetic susceptibilities as well as more comprehensive assessment of the complex economic, social and behavioural differences should be prioritised.
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Examining the Vitamin D Status of Children With Solid Tumors.
Juhász, O, Jakab, Z, Szabó, A, Garami, M
Journal of the American College of Nutrition. 2020;39(2):128-134
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Literature shows that 75% of the adult population worldwide experience vitamin D deficiency, of whom 13% fall under the category of extremely severe vitamin D deficiency (<10 ng/ml). The aim of this retrospective study was to compare the Vitamin D status of children with tumours or without. A secondary aim was to analyse the effects of vitamin D supplementation (as a complement to cancer treatment) on the vitamin D levels of children. The study included 173 children (males n=96; females n=77) aged between 0 and 18 who were treated for cancer. The control group consisted of 569 (males n=310; females n=259) children, aged 0 to 4 who received treatment at the clinic for reasons other than cancer. Results indicate that initial Vitamin D levels were significantly lower among children with cancer (19% lower than in the control group). A correlation between insufficient and deficient initial serum vitamin D levels and unfavourable prognosis was found. Authors suggest that vitamin D supplementation would be most efficient if medicine would follow the present trend of personalised therapy.
Abstract
Objective: Our aims were to compare the vitamin D status of children with and without cancer and to examine the possible correlation between vitamin D levels in children with cancer before initiating treatment and prognosis.Method: We compared the data of 173 children with cancer with those of 569 children without cancer.Results: We measured a significant difference (p = 1.34E-08) between the vitamin D levels of children with cancer before treatment and children without cancer. There was a significant correlation between the initial vitamin D levels of children with cancer and the prognosis (p = 0.016, odds ratio = 51.33) at 5% significance.Conclusions: The average vitamin D level was 19.76% lower in the population with cancer compared with the average of the control group, and we found a correlation between the lower vitamin D levels in children with cancer and the adverse prognosis. We suggest that supplying vitamin D is reasonable and a prospective study of vitamin D in pediatric patients with cancer is recommended.
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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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Comparison of Food and Nutrient Intakes between Japanese Dyslipidemic Patients with and without Low-Density Lipoprotein Cholesterol Lowering Drug Therapy: A Cross-Sectional Study.
Kameyama, N, Maruyama, C, Shijo, Y, Umezawa, A, Sato, A, Ayaori, M, Ikewaki, K, Waki, M, Teramoto, T
Journal of atherosclerosis and thrombosis. 2020;27(7):683-694
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Dyslipidaemia is a risk factor for atherosclerotic cardiovascular disease and its treatment is of great public health and clinical importance. The aim of this study was to investigate actual food and nutrient intakes in Japanese patients with dyslipidaemia who had not received dietary counselling. A secondary aim was to compare food and nutrient intakes between patients with and without low-density lipoprotein cholesterol (LDL-C) lowering drug therapy. This is a cross-sectional study of 104 (53 women & 51 men) dyslipidaemic patients with an age range from 30 to 65 years. Results show that most patients consumed excessive amounts of energy, lipids, saturated fatty acids, cholesterol and sodium, while consumption of dietary fibre, EPA and DHA were low, regardless of whether or not they were being treated with LDL-C lowering drugs. Furthermore, food groups showing an independent correlation with LDL-C concentrations differed between patients with and without LDL-C lowering drug therapy. Authors conclude that diet therapy while taking LDL-C lowering drugs, merits further consideration.
Abstract
AIM: We aimed to clarify actual food and nutrient intakes in Japanese patients with dyslipidemia. We also compared food and nutrient intakes between patients with and without low-density lipoprotein cholesterol (LDL-C) lowering drug therapy. METHODS Food and nutrient intakes were assessed employing 3-day weighted dietary records in this cross-sectional study of 104 Japanese outpatients with dyslipidemia, age 30-65 years, not given dietary counseling. Anthropometric and biochemical parameters were measured after an overnight fast. Food and nutrient intakes were compared between patients with versus without LDL-C lowering drug prescriptions. Stepwise multiple regression analysis was performed to identify relationships between the serum LDL-C concentrations and food intakes. RESULTS Of the 104 patients, 43.3% were prescribed LDL-C lowering drugs, primarily statins. Of the total patients, 83% had lipid intakes over 25% of total energy consumption (%E), exceeding the recommendation for dyslipidemia by the Japan Atherosclerosis Society. Similarly, 77% had saturated fatty acid intakes over 7%E, and 88% had cholesterol intakes over 200 mg per day. Dietary fiber consumption was low (<25 g) in 97% of patients. Those taking LDL-C lowering drugs consumed less "meat, poultry and processed meat products" and "cereals", and more "fish", "fruits" and "nuts", than patients not taking these drugs (p<0.05). Food intakes correlating with LDL-C concentrations independently of drug therapy differed between patients taking versus not taking these medications. CONCLUSION Our results support the necessity of diet therapy for patients with dyslipidemia regardless of whether LDL-C lowering drugs are prescribed.The clinical trial registration number: UMIN000022955.
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Proteomic profiles before and during weight loss: Results from randomized trial of dietary intervention.
Figarska, SM, Rigdon, J, Ganna, A, Elmståhl, S, Lind, L, Gardner, CD, Ingelsson, E
Scientific reports. 2020;10(1):7913
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Understanding biological substances, or "biomarkers" that are present in the body of individuals with obesity, could lead to personalised dietary recommendations for weight loss. Current research on biomarkers in individuals with obesity who have undergone a weight loss intervention is lacking. This secondary analysis of a randomised control trial study of 609 healthy and obese adults over 6 months, aimed to identify biomarkers associated with obesity, determine any changes with weight loss and if these could be used to make personalised recommendations. 263 biomarkers were tested and the results showed that 102 were associated with body mass index (BMI). 88 were elevated in individuals with a higher BMI. Upon weight loss, a large number of these decreased and a small number increased. The type of diet had no influence on how these biomarkers changed and only one could be used to predict weight loss. It was concluded that many of the biomarkers were connected to BMI and many changed with weight loss, however none of the biomarkers studied could be used to individualise dietary recommendations. This study could be used by healthcare professionals to understand that the role of biomarkers in personalising recommendations is complex and more research may be needed.
Abstract
Inflammatory and cardiovascular biomarkers have been associated with obesity, but little is known about how they change upon dietary intervention and concomitant weight loss. Further, protein biomarkers might be useful for predicting weight loss in overweight and obese individuals. We performed secondary analyses in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized intervention trial that included healthy 609 adults (18-50 years old) with BMI 28-40 kg/m2, to evaluate associations between circulating protein biomarkers and BMI at baseline, during a weight loss diet intervention, and to assess predictive potential of baseline blood proteins on weight loss. We analyzed 263 plasma proteins at baseline and 6 months into the intervention using the Olink Proteomics CVD II, CVD III and Inflammation arrays. BMI was assessed at baseline, after 3 and 6 months of dietary intervention. At baseline, 102 of the examined inflammatory and cardiovascular biomarkers were associated with BMI (>90% with successful replication in 1,584 overweight/obese individuals from a community-based cohort study) and 130 tracked with weight loss shedding light into the pathophysiology of obesity. However, out of 263 proteins analyzed at baseline, only fibroblast growth factor 21 (FGF-21) predicted weight loss, and none helped individualize dietary assignment.
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Very Low-Calorie Ketogenic Diet: A Safe and Effective Tool for Weight Loss in Patients With Obesity and Mild Kidney Failure.
Bruci, A, Tuccinardi, D, Tozzi, R, Balena, A, Santucci, S, Frontani, R, Mariani, S, Basciani, S, Spera, G, Gnessi, L, et al
Nutrients. 2020;12(2)
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Very low-calorie ketogenic diets (VLCKD) may be an effective way to lose weight. However, the high amount of protein they contain may harm the kidneys, especially in those who already have impaired kidney function. This observational study of 92 obese men and women aimed to evaluate the effect of VLCKD on weight loss in individuals with mild kidney failure, compared to healthy individuals. A VLCKD diet resulted in significantly decreased BMI and body weight, due to a decrease in fat mass and slight decrease in muscle mass. Improvements were seen in blood pressure, indicators for diabetes and cholesterol levels. No changes to kidney or liver function were apparent and only a few minor adverse events were reported. Interestingly a small percentage of individuals with mildly impaired kidney function reported improvements in their condition. It was concluded that VLCKD is a safe and effective way to lose weight in patients with obesity and mild kidney disease. This study could be used by healthcare professionals to consider recommending a VLCKD to patients who are obese and have mild kidney disease.
Abstract
Very low-calorie ketogenic diets (VLCKD) are an effective and increasingly used tool for weight loss. Traditionally considered high protein, ketogenic diets are often looked at with concern by clinicians due to the potential harm they pose to kidney function. We herein evaluated the efficacy and safety of a VLCKD in patients with obesity and mild kidney failure. A prospective observational real-life study was conducted on ninety-two patients following a VLCKD for approximately 3 months. Thirty-eight had mild kidney failure and fifty-four had no renal condition and were therefore designated as control. Anthropometric parameters, bioelectrical impedance and biochemistry data were collected before and at the end of the dietary intervention. The average weight loss was nearly 20% of initial weight, with a significant reduction in fat mass. We report an improvement of metabolic parameters and no clinically relevant variation regarding liver and kidney function. Upon stratification based on kidney function, no differences in the efficacy and safety outcomes were found. Interestingly, 27.7% of patients with mild renal failure reported normalization of glomerular filtrate after dietary intervention. We conclude that, when conducted under the supervision of healthcare professionals, a VLCKD is an effective and safe treatment for weight loss in patients with obesity, including those affected by mild kidney failure.
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Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease.
Smith, GI, Shankaran, M, Yoshino, M, Schweitzer, GG, Chondronikola, M, Beals, JW, Okunade, AL, Patterson, BW, Nyangau, E, Field, T, et al
The Journal of clinical investigation. 2020;130(3):1453-1460
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Non-alcoholic fatty liver disease (NAFLD) is a common complication of obesity and is associated with multiorgan insulin resistance, dyslipidaemia and an increased risk of diabetes and coronary heart disease. The aims of this study were to (a) determine hepatic de novo lipogenesis (DNL) [the liver’s biochemical process of synthesising fatty acids] in 3 distinct cohorts, (b) determine the relationships among hepatic DNL and intrahepatic [within the liver] triglyceride (IHTG) content, and (c) determine the effect of moderate (10%) weight loss. This study is a cross-sectional study which included a total of 67 men and women (mean age: 39 ± 1 years; 14 men and 53 women). Results highlight the importance of DNL in the pathogenesis of hepatic steatosis [build up of fats in the liver] and suggest that increases in daily 24-hour plasma glucose and insulin concentrations are major drivers of increased DNL in individuals with obesity and NAFLD. Additionally, moderate (10%) weight loss caused a marked decrease in both hepatic DNL and IHTG content. Authors conclude that increases in circulating glucose and insulin promote hepatic DNL in individuals with NAFLD. Whereas an improvement in insulin sensitivity and a decrease in hepatic DNL, are potentially important contributors to the decline in IHTG content associated with moderate weight loss.
Abstract
BACKGROUNDAn increase in intrahepatic triglyceride (IHTG) is the hallmark feature of nonalcoholic fatty liver disease (NAFLD) and is decreased by weight loss. Hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD. The physiological factors that stimulate hepatic DNL and the effect of weight loss on hepatic DNL are not clear.METHODSHepatic DNL, 24-hour integrated plasma insulin and glucose concentrations, and both liver and whole-body insulin sensitivity were determined in individuals who were lean (n = 14), obese with normal IHTG content (n = 26), or obese with NAFLD (n = 27). Hepatic DNL was assessed using the deuterated water method corrected for the potential confounding contribution of adipose tissue DNL. Liver and whole-body insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp procedure in conjunction with glucose tracer infusion. Six subjects in the obese-NAFLD group were also evaluated before and after a diet-induced weight loss of 10%.RESULTSThe contribution of hepatic DNL to IHTG-palmitate was 11%, 19%, and 38% in the lean, obese, and obese-NAFLD groups, respectively. Hepatic DNL was inversely correlated with hepatic and whole-body insulin sensitivity, but directly correlated with 24-hour plasma glucose and insulin concentrations. Weight loss decreased IHTG content, in conjunction with a decrease in hepatic DNL and 24-hour plasma glucose and insulin concentrations.CONCLUSIONSThese data suggest hepatic DNL is an important regulator of IHTG content and that increases in circulating glucose and insulin stimulate hepatic DNL in individuals with NAFLD. Weight loss decreased IHTG content, at least in part, by decreasing hepatic DNL.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGThis study was supported by NIH grants DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK52574 (Digestive Disease Research Center), and RR024992 (Clinical and Translational Science Award), and by grants from the Academy of Nutrition and Dietetics Foundation, the College of Natural Resources of UCB, and the Pershing Square Foundation.