-
1.
Banting Memorial Lecture 2021-Banting, banting, banter and bravado: Convictions meet evidence in the scientific process: Diabetes UK Professional Conference, 27 April 2021.
Lean, MEJ
Diabetic medicine : a journal of the British Diabetic Association. 2021;(11):e14643
Abstract
This personal account presents some glimpses into the clinical research processes which have made radical changes to our understanding of disease and treatment, and some characteristics of researchers, drawn from history and personal experiences around obesity and type 2 diabetes. Some summary messages emerge: The history of clinical diabetes research has shown how, perhaps through skilful leadership, combining very different personalities, skills and motivation can solve great challenges: Type 2 diabetes is a primary nutritional disease, secondary to the disease-process of obesity, not a primary endocrine disease. Type 2 diabetes is a manifestation of the disease-process of obesity, revealed by weight gain in people with underlying metabolic syndrome genetics/diathesis, mediated in large part at least by reversible ectopic fat accumulation impairing function of organs (liver, pancreas, brown adipose tissue). Treat overweight/obesity more seriously (defined as a disease-process with multiple organ-specific complications-not as a disease-state or BMI cut-off). Discuss the complications and risks of T2D openly: remission is as important as for cancers. Offer and support an optimal dietary weight management program as soon as possible from diagnosis, specifically aiming for remission: (a) Warn against non-evidence-based programs that look similar or claim to have similar potential: we have fully evidence-based programs; (b) Target sustained loss of >15 kg for Europeans (possibly less, e.g. >10 kg for Asians?). Increase future research support to enhance long-term weight loss maintenance. Several approaches need consideration: (a) Personalise diet compositions (recognising there is no intrinsic advantage from different carbohydrate/fat content). (b) Novel diet strategies (e.g. 5:2, time-restricted, flexible diet compositions). (c) New pharmaceutical agents as adjuncts to diet if necessary. (d) Novel food supplements to increase endogenous GLP-1 secretion.
-
2.
Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.
Montefusco, L, D'Addio, F, Loretelli, C, Ben Nasr, M, Garziano, M, Rossi, A, Pastore, I, Plebani, L, Lunati, ME, Bolla, AM, et al
Journal of endocrinological investigation. 2021;(11):2407-2415
-
-
Free full text
-
Abstract
BACKGROUND Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. AIM: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. METHODS Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. RESULTS After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1β, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. CONCLUSION Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.
-
3.
The use of Caralluma fimbriata as an appetite suppressant and weight loss supplement: a systematic review and meta-analysis of clinical trials.
Jayawardena, R, Francis, TV, Abhayaratna, S, Ranasinghe, P
BMC complementary medicine and therapies. 2021;(1):279
Abstract
BACKGROUND Obesity prevalence has increased during the past few decades, causing a pandemic with an influx in other co-morbidities. Many factors influence weight gain in an obesogenic environment therefore strategies for treating obesity may vary from conventional dietary and physical activity interventions to pharamacotherapy. A shift in unconventional strategies as herbal products for treating obesity have been investigated and one such plant extract is Caralluma fimbriata (C. fimbriata). Further, the studies included were systematically reviewed to gather evidence on potential effects of C. fimbriata as an appetite suppressant and weight loss supplement. METHODS A systematic review of clinical trials reporting the effects of C. fimbriata as appetite suppression and anti-obesity supplement was reported according to PRISMA guidelines. Data were obtained by searching three databases: PubMed®, Web of Science® and SciVerse Scopus® for studies published until 30th April 2020. RESULTS A total of 7 articles studying C. fimbriata satisfied the inclusion and exclusion criteria and were sourced from various countries including Australia (3), Cuba (1), India (2) and Spain (1). Almost all studies recruited adults who were overweight or obese with a BMI > 25 kg/m2 (n = 5), with the exception of two studies, one that recruited healthy adults with a BMI average of 26.5 kg/m2 and the second one utilised a population of children and adolescents with Prader-Willis Syndrome (PWS). Parameters assessing obesity, biochemical and appetite factors were analysed by carrying out a meta-analysis. Compared to placebo controlled group, C. fimbriata extract significantly reduced WC by 1.59 cm (95% CI, - 3.07 to - 0.10, p = 0.041) and WHR by 0.06 (95% CI, - 0.12 to - 0.01, p = 0.05) although no significant effects were seen on BW, BMI and HC. Biochemical and appetite parameters outcome on C. fimbriata consumption had no significant changes. Any side effects of individuals who ingested the extract were reported by few studies of which most common effects were constipation, diarrhoea, nausea and rashes. CONCLUSION Appetite parameters showed no significant changes and metabolic parameters did not improve with C.fimbriata supplementation therefore it is unlikely to recommend C. fimbriata as a weight loss supplement and an appetite suppressant.
-
4.
Levels of Circulating miR-122 are Associated with Weight Loss and Metabolic Syndrome.
Hess, AL, Larsen, LH, Udesen, PB, Sanz, Y, Larsen, TM, Dalgaard, LT
Obesity (Silver Spring, Md.). 2020;(3):493-501
Abstract
OBJECTIVE This study investigated whether the levels of specific serum microRNAs (miRNAs) were altered following diet-induced weight loss and whether the serum miRNAs differed in the presence of the metabolic syndrome. METHODS The study was a weight loss intervention trial with a prescribed energy deficit of approximately 500 kcal/d. Levels of 22 miRNAs were determined in serum samples from 85 participants with overweight or obesity. miRNAs were analyzed using TaqMan Array miRNA Cards and normalized to the geometric mean of spiked-in ath-miR-159a and U6 small nuclear RNA using the ΔCT method. RESULTS The average weight loss was 5.7 kg (P < 0.001). miR-122-5p (-0.18 ± 0.06 log fold relative to initial, P < 0.01) and miR-193a-5p (-0.12 ± 0.04, P < 0.01) levels decreased in response to weight loss. miR-126a-3p (0.11 ± 0.04, P = 0.01) and miR-222-3p (1.51 ± 0.12, P < 0.001) levels increased. Furthermore, a higher level of miR-122-5p was observed at baseline in participants with the metabolic syndrome compared with participants without (0.28 ± 0.08, P < 0.01). CONCLUSIONS Changes in circulating miR-122-5p, miR-126a-3p, miR-193a-5p, and miR-222-3p in response to diet-induced weight loss are demonstrated. Furthermore, assessment of miR-122-5p could be an indicator of an adverse metabolic health status independent of obesity.
-
5.
A Single Motivational Lecture Can Promote Modest Weight Loss: A Randomized Controlled Trial.
Nakata, Y, Sasai, H, Tsujimoto, T, Hashimoto, K, Kobayashi, H
Obesity facts. 2020;(2):267-278
Abstract
BACKGROUND Obesity is a public health problem worldwide. To widely disseminate weight-loss interventions across the target population, a cost-effective approach is needed. OBJECTIVE We aimed to test whether a single motivational lecture could promote weight loss. METHODS Our study was a 3-month randomized controlled trial, and we recruited participants via local newspaper advertisements in 3 cities in Ibaraki Prefecture, Japan, and randomly assigned them to a control group (no intervention) and an intervention group, who attended a single motivational lecture lasting approximately 2 h. No other lectures or textbooks were provided. The eligibility criteria included an age of 40-64 years, a body mass index (BMI) of 25-40 kg/m2, and the presence of at least 1 component of metabolic syndrome. The primary outcome was body weight change at 3 months. RESULTS We enrolled 145 eligible participants with a mean age of 53.8 ± 7.1 years and a BMI of 28.5 ± 3.1 kg/m2. The 3-month body weight change in the control and intervention groups was -0.65 kg (95% confidence interval [CI] -1.09 to -0.20) and -2.48 kg (95% CI -3.01 to -1.95), respectively. The between-group difference was 1.83 kg (95% CI 1.15-2.51). CONCLUSIONS The significant difference suggested that a single motivational lecture is an effective option to promote modest weight loss in the short term.
-
6.
DNA methylation markers in obesity, metabolic syndrome, and weight loss.
Samblas, M, Milagro, FI, Martínez, A
Epigenetics. 2019;(5):421-444
-
-
Free full text
-
Abstract
The fact that not all individuals exposed to the same environmental risk factors develop obesity supports the hypothesis of the existence of underlying genetic and epigenetic elements. There is suggestive evidence that environmental stimuli, such as dietary pattern, particularly during pregnancy and early life, but also in adult life, can induce changes in DNA methylation predisposing to obesity and related comorbidities. In this context, the DNA methylation marks of each individual have emerged not only as a promising tool for the prediction, screening, diagnosis, and prognosis of obesity and metabolic syndrome features, but also for the improvement of weight loss therapies in the context of precision nutrition. The main objectives in this field are to understand the mechanisms involved in transgenerational epigenetic inheritance, and featuring the nutritional and lifestyle factors implicated in the epigenetic modifications. Likewise, DNA methylation modulation caused by diet and environment may be a target for newer therapeutic strategies concerning the prevention and treatment of metabolic diseases.
-
7.
An integrated transcriptomic and epigenomic analysis identifies CD44 gene as a potential biomarker for weight loss within an energy-restricted program.
Samblas, M, Mansego, ML, Zulet, MA, Milagro, FI, Martinez, JA
European journal of nutrition. 2019;(5):1971-1980
Abstract
PURPOSE The interindividual variable response to weight-loss treatments requires the search for new predictive biomarkers for improving the success of weight-loss programs. The aim of this study is to identify novel genes that distinguish individual responses to a weight-loss dietary treatment by using the integrative analysis of mRNA expression and DNA methylation arrays. METHODS Subjects from Metabolic Syndrome Reduction in Navarra (RESMENA) project were classified as low (LR) or high (HR) responders depending on their weight loss. Transcriptomic (n = 24) and epigenomic (n = 47) patterns were determined by array-based genome-wide technologies in human white blood cells at the baseline of the treatment period. CD44 expression was validated by qRT-PCR and methylation degree of CpGs of the gene was validated by MassARRAY® EpiTYPER™ in a subsample of 47 subjects. CD44 protein levels were measured by ELISA in human plasma. RESULTS Different expression and DNA methylation profiles were identified in LR in comparison to HR. The integrative analysis of both array data identified four genes: CD44, ITPR1, MTSS1 and FBXW5 that were differently methylated and expressed between groups. CD44 showed higher expression and lower DNA methylation levels in LR than in HR. Although differences in CD44 protein levels between LR and HR were not statistically significant, a positive association was observed between CD44 mRNA expression and protein levels. CONCLUSIONS In summary, the combination of a genome-wide methylation and expression array dataset can be a useful strategy to identify novel genes that might be considered as predictors of the dietary response. CD44 gene transcription and methylation may be a possible candidate biomarker for weight-loss prediction.
-
8.
Evaluations of Lifestyle, Dietary, and Pharmacologic Treatments for Pediatric Nonalcoholic Fatty Liver Disease: A Systematic Review.
Mann, JP, Tang, GY, Nobili, V, Armstrong, MJ
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(8):1457-1476.e7
Abstract
BACKGROUND & AIMS There are no approved treatments for pediatric nonalcoholic fatty liver disease (NAFLD) and there is a lack of consensus on the best outcome measure for randomized controlled trials. We performed a systematic review of treatments tested for pediatric NAFLD, the degree of heterogeneity in trial design, and endpoints analyzed in these studies. METHODS We searched publication databases and clinical trial registries through January 7, 2018 for randomized controlled trials (published and underway) of children (<18 years) with NAFLD. We assessed improvements in histologic features, radiologic and biochemical markers of reduced fibrosis, metabolic syndrome parameters, and adverse events. The quality of the trials was assessed using a modified version of the Cochrane risk of bias tool. RESULTS Our final analysis included 21 randomized controlled trials, comprising 1307 participants (mean age, 12.6 years; 63% male; mean duration of intervention, 8 months). Most studies evaluated weight loss with lifestyle intervention (n=8), oral polyunsaturated fatty acid treatment (PUFAs, n=6), or oral antioxidant treatment (n=7). Biomarkers of NAFLD decreased with weight loss, but most studies did not include histologic data. Trials of antioxidants were heterogeneous; some reported reduced histologic features of steatohepatitis with no effect on triglycerides or insulin resistance. PUFAs and probiotics reduced radiologic markers of steatosis, insulin resistance, and levels of triglycerides. Only 38% of the trials had biopsy-proven NAFLD as an inclusion criterion. There was heterogeneity in trial primary endpoints; 10 studies (48%) used levels of aminotransferases or ultrasonography findings as a primary endpoint and only 3 trials (14%) used histologic features as the primary endpoint. We identified 13 randomized controlled trials that are underway in children with NAFLD. None of the protocols include collection of liver biopsies; 9 trials (69%) will use magnetic resonance imaging quantification of steatosis as a primary outcome. CONCLUSIONS In a systematic review of published and active randomized controlled trials of children with NAFLD, we found a large amount of heterogeneity in study endpoints and inclusion criteria. Few trials included histologic analyses. Antioxidants appear to reduce some features of steatohepatitis. Effects of treatment with lifestyle modification, PUFAs, or probiotics have not been validated with histologic analysis. Trials that are underway quantify steatosis magnetic resonance imaging-outcomes are anticipated.
-
9.
How much does reduced food intake contribute to cancer-associated weight loss?
Martin, L, Kubrak, C
Current opinion in supportive and palliative care. 2018;(4):410-419
Abstract
PURPOSE OF REVIEW An international consensus group defined cancer cachexia as a syndrome of involuntary weight loss, characterized by loss of skeletal muscle (with or without fat loss), which is driven by a variable combination of reduced food intake and altered metabolism.This review presents recent studies that evaluated the contribution of reduced food intake to cancer-associated weight loss. RECENT FINDINGS Four studies examined food intake in relation to weight loss. Heterogeneity among studies rendered aggregation and interpretation of results challenging. Despite these limitations, reduced food intake had consistent significant, independent associations with weight loss. However, reduced food intake did not explain all the variation in weight loss; and limited data suggests factors related to alterations in metabolism (e.g. increased resting energy expenditure, systemic inflammation) are also contributing to weight loss. SUMMARY Reduced food intake is a significant contributor to cancer-associated weight loss. Understanding the magnitude of the association between food intake and weight loss may improve when it is possible to account for alterations in metabolism. Efforts to align clinical assessments of food intake to reduce heterogeneity are needed.
-
10.
Effect of carbohydrate restriction-induced weight loss on aortic pulse wave velocity in overweight men and women.
Syed-Abdul, MM, Hu, Q, Jacome-Sosa, M, Padilla, J, Manrique-Acevedo, C, Heimowitz, C, Parks, EJ
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2018;(12):1247-1256
Abstract
Increased aortic stiffness, measured by carotid-to-femoral pulse wave velocity (PWV), is an independent predictor of cardiovascular disease, and past data have shown that low-fat and low-energy diets, fed for 8-24 weeks, lower PWV. The purpose of this study was to determine whether a reduction in PWV would be achieved by dietary carbohydrate (CHO) restriction, shown to bring about weight loss over a shorter timeframe. Men (n = 10, age: 41.8 ± 10.2 years, BMI: 34.2 ± 3.0 kg/m2 (mean ± SD)) and women (n = 10, age: 38.6 ± 6.1 years, BMI: 33.5 ± 3.8 kg/m2) with characteristics of insulin resistance and the metabolic syndrome consumed a structured, CHO-restricted diet for 4 weeks (energy deficit, 645 kcal/day). For the whole group, subjects lost 5.4% ± 0.5% (P < 0.001) of body weight and experienced significant reductions in blood pressure (6%-8%), plasma insulin (34%), and triglycerides (34%). PWV was reduced by 6% ± 2% (7.1 ± 0.2 m/s to 6.7 ± 0.2 m/s, P = 0.008) and surprisingly, in women, it fell significantly (from 7.2 ± 0.3 m/s to 6.3 ± 0.3 m/s, P = 0.028), while no changes were observed in men (7.2 ± 0.3 vs. 7.0 ± 0.3 m/s, P = 0.144). This is the first study to demonstrate that weight loss can improve PWV in as little as 4 weeks and that dietary CHO restriction may be an effective treatment for reducing aortic stiffness in women. Future studies are needed to establish the mechanisms by which dietary CHO restriction may confer more cardiovascular benefits to women than to men.